CENTER FOR EARLY DIAGNOSIS AND THERAPY RESEARCH ON
NEURODEGENERATIVE DISEASES
– A SWEDISH NETWORK
ANNUAL REPORT JULY 2012 – JUNE 2013
Table of Content
Page
Wordings from the Director
3
Summary
4
Background & Objectives
5
Outcome & Major Achievements
6
External Collaboration
9
Organisation and infrastructure
11
List of Core Coordinators and other members
13
Information Dissemination
17
Research Budget Allocation
19
Swedish Brain Power in Future
21
List of Research Projects
22
Publication List
25
2
Wordings from the Director
Swedish Brain Power has now been a part of the
scientific community for eight years. During this
time, public interest in how our brain works has
grown in pace with the brain research made
progress. It is a young and very exiciting research
area and a “hot topic” in many contexts. People
are eager to know how one can prevent dementia
using everything from food to meditation.
This increasing interest in brain functions and characteristics at an individual level is very
satisfying. Unfortunately it has not yet been followed by an equally strong interest in how to
prevent the health threat of dementia on a societal and community level. According to
WHO's latest report, dementia is now the fastest growing public health disease in the world
and will cost huge amounts if nothing is done. Swedish Brain Power has tried to draw
attention to this in the public debate, including opinion articles in the press and on the web.
If we look at the Swedish Brain Power's purely scientific contributions, the list of new
discoveries and the amount of published scientific papers in this report, speaks for
themselves. The research collaboration across both disciplinary and geographical boundaries
has given an added value that is greater than we could ever hope for. Swedish Brain Power is
now an established research network and an important contributor to neurobiological
research.
For us it is clear that dementia research is underfunded relative to what dementia costs
society in both suffering and money. Let us hope that awareness of this increase with the
interest in the brain itself. In other words, our mission is both social and scientific. I am
optimistic for the simple reason that anything else would be a disaster.
Finally, I would like to thank our board and our founder, Knut & Alice Wallenberg
Foundation, for their unfailing interest and valuable support.
Bengt Winblad
3
Summary
The Swedish Brain Power (SBP) program started in summer 2005. From July 2010, Knut &
Alice Wallenberg (KAW) Foundation is the sole sponsor for a 5 year period. SBP focuses on
research for early diagnosis and treatment of neurodegenerative disorders and has become
a well-established leading national research network.
Collaboration
To increase the interaction between the national experts in the neurodegenerative area was
one of the main goals for the SBP program. This has by far been reached; The Swedish Brain
Power researchers have obtained a genuine understanding, collaboration and interaction
between all involved research groups, as well as individual researchers.
SBP researchers are to a great extent collaborating with our Nordic neighbouring countries,
such as the establishment of a Nordic collaborative academic program, and several
collaborative experimental research projects with research groups in Oslo, Stavanger,
Copenhagen and Kuopio. In addition, SBP researchers have extensive collaboration with
both pharma and biotech industry, both on individual levels and in clinical trials where the
SBP clinical trial centers are first-choice worldwide for new, innovative clinical trials.
The SBP initiated quality registry (SveDem) now comprises approx 40 000 new registrations
of patients (out of which 24 000 from Primary Care), the figure for follow-up’s is 16 000 from
Specialist settings respectively 11 000 from Primary Care. The registry currently includes 74%
of all Primary Care Units in Sweden and 95% of all Geriatric Specialist Clinics. SveDem is the
data source for several quality indicators in dementia care. A large number of research
projects and publications are based on this registry.
Through SBP, we have been able to establish joint bio banks all over Sweden including
material from patients with Alzheimer Disease (AD), Parkinson Disease (PD), Amyotrophic
Lateral Sclerosis (ALS) and healthy controls (cerebrospinal fluid (CSF), fibroblasts, blood,
brains, DNA). SBP researchers are closely collaborating with the StratNeuro strategic
research program including Karolinska Institutet, the Royal Institute of Technology (KTH) and
the SBP members from Umeå University.
Scientific outcome
During the 8th year, 57 research projects resulted in totally 150 peer reviewed articles (81
within the clinical platform, 49 basic research platform and 20 within the
caring/rehabilitation platform). All research projects are listed on pp 22-24 and all
publications on pp 25-37.
A summary of our major achievements can be found on pages 6-9 and a more descriptive
summary of all on-going research projects is attached (attachment 1) to this report.
SBP researchers continue to receive prestigious awards for their contribution to the research
field. To mention some, this year Prof Laura Fratiglioni was awarded the “International
Alzheimer Association Lifetime Achievement Award in Prof Bengt Winblad’s name”, Prof Kaj
4
Blennow received a remarkable European price “Fondation sur la recherché sur Alzheimer”,
the Eric K Fernström’s award was given to Prof Martin Hallbeck and the “Eric & Waijlit
Forsgrens pris” to Prof Agneta Nordberg.
The Swedish Brain Power Program –
Background & Objectives
The Swedish Brain Power (SBP) program was established in July 2005, thanks to the initiative
from the foundations Invest in Sweden Agency (ISA), KK Foundation, Foundation for
Strategic Research, Vårdal Foundation, Knut & Alice Wallenberg Foundation and VINNOVA.
From July 2010, the SBP program is sponsored by KAW for another 5 years (2010-2015) with
in total 100 million SEK.
The network is formed by the Swedish leading research groups in the field of
neurodegenerative disorders with a main focus on ALS, Alzheimer and Parkinson disease.
Through SBP, in-depth collaboration has been established between groups that rarely or not
at all earlier used to collaborate. The SBP research program spans from basic to clinical,
epidemiological and caring research. The organisation is outlined in order to facilitate and
encourage collaboration between the involved research groups. The prioritization of
developing translational research has also created many contacts and new collaborations
between academic research and industry. It is an incentive for the program to keep the
administrative costs as low as possible, and focus our efforts on research.
The overall aim for the SBP network is to improve early diagnosis, treatment and care of
patients affected by neurodegenerative diseases (Alzheimer and Parkinson disease,
Amyotrophic Lateral Sclerosis). These often age-related diseases are a growing public health
problem worldwide due to increased elderly population. There is a great need for new and
more effective treatments for dementia and other neurodegenerative diseases, and for
increased knowledge on how to give the best possible care.
SPECIFIC OBJECTIVES
To increase our knowledge regarding the pathogenesis of neurodegenerative diseases
To validate the basic research target findings in cell and animal models
To translate our basic research on biomarkers in order to improve diagnostic accuracy
and identify adequate target populations for intervention
To identify new mutations and risk genes
To further identify and validate preventive strategies and initiate prevention trials
To validate different treatment strategies in preclinical phases
To achieve efficacious treatment of neurodegenerative diseases on a personalized
basis
To develop new instruments for improved measurement of intervention/treatment
effects as well as new caring strategies; eg environmental and psychosocial.
5
Outcome & Major Achievements
In our continuous efforts to contribute to an accurate early diagnosis of neurodegenerative
disorders, we have found that AD mutation carriers showed high regional PIB retention
fifteen years before expected age of onset while. Also astrocytosis appears to be an early
phenomenon in FAD pathology, preceding with years the deposition of fibrillar amyloid. In
MRI studies, we have shown that depressed AD patients had significantly larger atrophy in
the medial and lateral temporal cortex compared to non-depressed AD. The levels of 24Shydroxycholesterol in the circulation have also been found to reflect cholesterol metabolism
in the brain, and increased in an early stage of a neurodegeneration.
New methodologies have been developed for improved diagnosis and care. A semiautomatic method for segmentation of the transentorhinal region in the perirhinal cortex
has been reported. Automated methods for both MRI and CT images resulted in absolute
values comparable to manually delineated volumes, which encourages to further validate
our proposed algorithm in larger datasets of CT images. New methods for exact
quantification of synaptic proteins in CSF by mass spectrometry and for quantification
(antibody-free) of APP isoforms in human CSF have been developed.
A new instrument for early detection of problems in daily living that includes ADL, leisure
and work has been developed. The instrument is aimed for primary care, needs limited
education time and seems valid for detecting early ADL problems in dementia. In addition,
another new instrument for assessing medical decision-making (LIMD) to be used as
research tool has been validated.
Implementation studies in care resulted in a generic model for national guidelines into
nursing homes and other types of care facilities for persons with dementia disorders. Studies
have been performed showing that residents with dementia in more person-centred units
had a higher quality of life and better ability to perform activities of daily living.
Epidemiological studies have reported that cognitive impairment is frequent (73%), often
previously undetected and associated with a three-fold increase in mortality risk. Also,
prevalence of dementia was stable from the late 1980s to the early 2000s in central
Stockholm, Sweden, whereas survival of patients with dementia increased. These results
suggest that incidence of dementia may have decreased during this period.
In clinical trials, we have been able to show that encapsulated NGF cell therapy to the basal
forebrain in ten patients with increasing dose is safe and well tolerated with improved
cognition in a subset of patients. Cognitive responders to the NGF treatment show increased
cholinergic activity.
Cost-effectiveness studies reported that the main reasons for the higher costs with Disease
Modifying Treatment (DMT) were the costs of DMT itself and the prolonged survival with
DMT. But - even if costs increase with DMT, the model indicates cost effectiveness.
6
A large number of novel findings in disease mechanisms have been published, including new
genetic findings and possible disease targets;
- In frontotemporal dementia and amyotrophic lateral sclerosis, a novel mechanism of nonATG initiated translation in C9orf72 mutation carriers was found. This mechanism leads to
an intraneuronal aggregation of poly-dipeptides especially in the cerebellum and can be
detected by a method called C9RANT. Another study showed that EPHA4 is a disease
modifier of ALS both in animal models and in humans.
- In Parkinson disease (PD), the rs9722 polymorphism in the S100B gene was significantly
associated with age of onset in two separate populations with totally 1500 individuals.
- We have shown that removal of PTEN, which disinhibits Akt, increases the neurite growth
potential of neurons in mice. When embryonic PTEN-KO Dopaminergic neurons are grafted
to MitoPark mice, they survive and function better than wild type embryonic neurons,
leading to structural, electrophysiological and behavior improvements. This suggests one
way in which dopaminergic neuron grafts may become more effective therapeutic tools.
- Of important for PD mechanisms, another study showed that both monomers and
oligomers of α-synuclein transfer from neuron to neuron via neuritic connections. However,
the efficacy of transfer seems to differ between different species, α-synuclein-related
pathology occurs largely independently from LRRK2 expression, at least within neurons of
the mouse hindbrain. LRRK2 has an important role in adult neurogenesis, in particular in
neuronal morphogenesis.
- In Alzheimer disease (AD) novel findings demonstrated that the amyloid beta peptide (Aβ)
can influence the number of contact points between mitochondria and the endoplasmic
reticulum.
- Also, a new mediator of AD pathology has been found. Trx80, truncated form of trx1 acts
as an Aβ-antiaggregant. Moreover measuring Trx80 in CSF discriminates AD from MCI and
control patients.
- Another study reported that levels of the SPM lipoxin A4 (LXA4) were reduced in both CSF
and hippocampus from AD-patients, and correlated with tau phosphorylation and minimental state examination (MMSE) score. This study suggests that in AD there is an
impairment of the resolution phase of neuroinflammation.
- Studies of ageing have shown that in humans there is a link between lower dopamine D1
receptor densities in neocortical regions and higher within-person variability during a task
assessing the ability to deal with cognitive interference. Another report has demonstrated
that germline mitochondrial DNA mutations per se aggravate ageing. Thus, there are genetic
risk factors for ageing located outside of the regular genome, and inherited exclusively from
the mother.
7
PUBLICATIONS
We have published 150 original articles including:
Eighteen (18) publications with an impact factor 7-15 (12%), published in Neurology, Brain,
Hum Mol Gen, Ann Neurol, Eur Hear J, Hum Brain Map, J Neurosci, PNAS, and EMBO Mol
Med
and
Eight (8) publications with an impact factor 15-20 (~5%), published in Nat Med, Nat Gen,
Nature, Nat Neurosci, Nat Methods and BMJ
DISSERTATIONS
A total of 11 SBP PhD students defended their thesis this year:
1. Lena Johansson on Psychological stress in relation to dementia and brain structural
changes, September 14, 2012
2.
Eva Lindqvist on Assistive technology as cognitive support in everyday life for persons
with dementia or stroke, September 14, 2012
3.
Jaime M Ross on Mitochondrial DNA mutations. Brain developmental and ageing
consequences, and possible treatments, September 28, 2012
4.
Johanna Wanngren on Molecular studies of the γ-secretase complex: Focus on genetic
and pharmacological modulations, October 5, 2012
5.
Tobias Karlsson on Nogo receptors, plasticity and lasting memories, November 16, 2012
6.
Annelie Pamrén on Different types of γ-secretase complexes and their effect on
substrate processing, December 7, 2012
7.
Erik Olsson on Volumetric assessment of hippocampus and cerebral white matter lesions
in structural MRI, January 21, 2013
8.
Debora Rizzuto on Living longer than expected: protective and risk factors related to
human longevity, February 8, 2013
9.
Caroline Ingre on the aetiology of ALS: a comprehensive genetic study, April 17, 2013
10. Daniel Sjölie on Human brains and virtual realities, computer-generated presence in
theory and practice, May 17, 2013
11. S Savage on the role of forebrain cholinergic innervation for phencyclidine-induced
behaviors and gene expression patterns, June 4, 2013
8
External Collaboration
NATIONAL & INTERNATIONAL EXTERNAL COLLABORATION (ie outside SBP)
Except for the internal collaboration between involved SBP research groups, the individual
SBP researchers are involved in a number of EU projects. The national and especially
international collaborations are extensive. In addition, we are also to a great extent
collaborating with industry. All collaboration agreements are on individual level with the
involved SBP researcher.
Below are listed a number of our collaborations;
-
EU projects
o EU-FP7 INMIND
o EU-JPND BIOMARKAPD
o FTD consortium (GWAS), Early onset dementia consortium & the GENFI group
o CLINIGENE (the NGF study was included)
-
National Academic collaboration
o Malmö Diet and Cancer study
o FAS Epi Life Center, Gothenburg (www.epilife.sahlgrenska.gu.se)
o StratNeuro program at Karolinska Institutet
o Dept of Clinical Neuroscience, Dept of Mol Medicine and Surgery, Karolinska
Institutet
o KTH (Royal Institute of Technology)
o Luleå University, Stockholm University (Stress Research Center), Umeå
University, Lund University (Radiology section)
o Wallenberg Neuroscience Center, Lund
-
International Academic collaboration
o Genetic Epidemiology of Parkinson Disease (GEO-PD)
o Norway: MedCoast (Gothenburg-Oslo MCI study), Oslo Univ (Kirkevold)
o Finland: Åbo Akademi Univ (Laine), Turku Univ (Rinne), Univ of Eastern Finland,
Kuopio (Koistinaho, Soininen)
o Germany: DZNE, Magdeburg (Lindenberger), Tübingen Univ, Dept of Neurology
(Schule, Schöls), Hertie Inst for Clin Brain Research, Tübingen (Gasser, Biskup),
Max Planck Institute for Biology of Ageing (NG Larsson)
o Belgium: Leuven Univ, Dept of Molecular and Developmental Genetics (de
Strooper)
o The Netherlands: VUMc, Amsterdam (Scheltens, Visser), Maastricht Univ
(Verhey, Handels)
o Italy: Univ of Bologna (Rimondini, Atti), Univ of Florence, Dept Neurology
(Pantoni), Univ of Brescia, Clin & Med Exp Science
o Spain: Univ of Oviedo (Gutierrez)
o France: Inserm Centre for research in epidemiology and population health,
Univ of Bourgogne (Bretillon)
o McGill Univ Canada (Cuello), UVic, Canada (Mac Donald)
o Dept of Biomedical Engineering, Univ of Alberta, Edmonton, Canada
9
o South Carolina Univ (Granholm), Brown Univ (Wahlberg), Mayo Univ,
Alzheimer Disease Research Center (eg Bienek), Rockefeller Univ (Sakmar),
Brigham Young Univ, Utah, Cornell Univ, New York, La Trobe Univ (Taylor)
o Lab of Genetics, NIA & NIH, Bethesda (Cookson, Dillman)
o La Trobe Univ, Australia
o Japan: Kobe Univ (Tanemura), RIKEN Brain Institute (Saido, Nilsson)
-
Industrial
o GE Healthcare
o Bayer Pharma
o DiaGenic
o NsGene A/S
o Hoffmann-La Roche
o AstraZeneca
o Boehringer-Ingelheim
o Gyros AB, Uppsala
o BioArctic, Stockholm
Furthermore, a large number of clinical trials, sponsored by the pharma industry, are
performed at the three involved clinics on the SBP prioritized diseases: ALS, Alzheimer and
Parkinson diseases. These include both studies for drug development and on biomarkers for
diagnosis.
10
Organisation and infrastructure
One main goal with the Swedish Brain Power network is to facilitate and encourage efficient
interdisciplinary collaboration in order to take advantage of the partners’ expertise and
achieve best possible research outcome. In a legal aspect, Swedish Brain Power is a Center of
Excellence within Karolinska Institutet (KI) with collaborators all over Sweden. The
Coordination Unit is located at the KI Center for Alzheimer Research, Department NVS,
Karolinska Institutet. SBP is directed by Prof Bengt Winblad, together with Maria Eriksdotter
as co-Director and Gunilla Johansson as Coordinator.
The SBP work is structured into three research platforms; Clinic-Epidemiology, Basic and
Caring/Technology platforms (green, blue, lilac in the figure below). Each platform is formed
by several cores; eg pre-clinics & transgenic models, epidemiology, care/caring &
rehabilitation. Since “Ethics” concerns all research areas, this core is placed within the
middle circle. Each core consists of research groups from the involved universities, and is
headed by scientific core coordinators, who in turn form a Steering Committee.
The SBP Organisation Plan
Leadership and coordination
SBP is led by a Governing Board with representatives from eg the founder, academia,
industry and county council. The Board takes a global responsibility for the SBP program,
takes the final decision on research activities and allocation of the budget, and makes the
policy decisions. The Board members also act as ambassadors for the program and strive to
attract additional funding and industrial collaboration. The Governing Board meets at least
once per term, and additional times if required.
11
Governing Board
Håkan Eriksson, Chair
Agneta Holmäng, Göteborg
Christer Köhler, Stockholm
Staffan Normark, Stockholm
Olle Stendahl, Linköping
Göran Stiernstedt, Stockholm
Co-opted members of the Governing Board
Kerstin Tham/Angel Cedazo Minguez, Head/Acting Head of NVS Dept, KI
Bengt Winblad, Director SBP
Maria Eriksdotter, Co-Director SBP
Gunilla Johansson, Coordinator SBP
During year 8, the Governing Board met twice; in December 2012 and in May 2013.
Steering Committee
The Steering Committee (SC) consists of all core coordinators (see list next page). The SC
deals with more specific issues, such as scientific activities including a first evaluation of the
research projects to be presented to the Board for decision. The SC usually meets 1-2 times
per term, last year in October 2012 and April 2013.
Executive Group
The Executive Group deals with the daily decisions and consists of Director Bengt Winblad,
Co-Director Maria Eriksdotter and Coordinator Gunilla Johansson. Since Maria Eriksdotter
will be the new Head of the Dept NVS from August 1, Angel Cedazo Minguez will replace her
as Co-Director from that date.
SBP PhD’s and PhD students
Currently, 39 postdocs, 22 registered PhD students and 13 research nurses/technicians
obtain salary support from the program. In addition, all 25 core coordinators & approx 40
postdocs/others are partly involved in the research projects without any funding from SBP.
All collaborators are listed on page 14-17.
During year 8, eleven PhD students have defended their thesis;
Lena Johansson, ARC KI Solna, Eva Lindqvist, KI Huddinge, Jaime Ross, KI Solna, Johanna
Wanngren, KI Huddinge, Tobias Karlsson, KI Solna, Anneli Pamrén, KI Huddinge, Erik Olsson,
Gothenburg, Deborah Rizzuto, ARC KI Solna, Caroline Ingre, Umeå, Daniel Sjölie, Umeå and S
Savage, KI Solna.
12
SWEDISH BRAIN POWER – Core Coordinators and Other Members
Director: Bengt Winblad, Professor
Co-Director: Maria Eriksdotter, Professor
Coordinator: Gunilla Johansson
Communication Manager: Annbritt Ryman
Core
Coordinators
Other Members
Diagnostics and Therapeutic research,
Clinical Trial Center
Karolinska Institutet, Stockholm
Agneta Nordberg, Professor
Karolinska Institutet, Stockholm
Niels Andreasen, MD, PhD
Maria Eriksdotter, Professor, MD
Dag Aarsland, Professor, MD
Ove Almkvist, Professor
Taher Darreh-Shori, PhD
Amelia Marutle, PhD
Elena Rodriguez-Vieitez, PhD
Karim Farid, PhD
Larysa Voytenko, PhD
Erik Hjorth, PhD
Helga Eyjolfsdottir, PhD stud
Ruiqing Ni, PhD stud
Sara Garcia-Ptacek, PhD stud
Skåne University Hospital, Malmö
Lennart Minthon, Professor
Skåne University Hospital, Malmö
Elisabet Londos, Assoc Prof, MD
Katarina Nägga, MD, PhD
Oskar Hansson, MD, PhD
Erik Stomrud, PhD
Gustav Torisson, PhD stud
Malin Lavesson, RN
Sahlgrenska Academy, Univ of
Gothenburg
Anders Wallin, Professor
Sahlgrenska Academy, Univ of
Gothenburg
Arto Nordlund, PhD
Erik Olsson, PhD
Carl Eckerström, PhD
Michael Jonsson, PhD
Maria Bjerke, PhD
Annika Öhrfelt, PhD
Niklas Klasson, PhD stud
Mårten Carlsson, PhD stud
Eva Bringman, research nurse
Uppsala University
Lars Lannfelt, Professor
Uppsala University
Martin Ingelsson, Assoc Prof
Joakim Bergström, PhD
Hedvig Welander, PhD
Lund University
Gunnar Gouras, Professor
Lund University
Patrik Brundin, Professor
Sonia George, PhD
Mathilde Faideau, PhD
13
Epidemiology
Karolinska Institutet,Stockholm
Laura Fratiglioni, Professor
Sahlgrenska Academy, Univ of
Gothenburg
Ingmar Skoog, Professor
Neuropsychology
Karolinska Institutet, Stockholm
Lars Bäckman, Professor
University of Gothenburg
Boo Johansson, Professor
Umeå University
Lars Nyberg, Professor
Care Research,
Rehabilitation
Karolinska Institutet, Stockholm
Miia Kivipelto, Professor
Hui-Xin Wang, PhD
Chengxuan Qiu, PhD
Lina Rosvall, PhD
Barbara Caracciolo, PhD
Weili Xu, PhD
Sahlgrenska Academy, Univ of
Gothenburg
Pernille Olesen, PhD
Hanna Falk, PhD
Svante Östling, PhD
Simona Sacuiu, PhD
Karolinska Institutet, Stockholm
Marc Gitart-Masip, PhD
Göran Papenberg, PhD
Erika Jonsson Laukka, PhD
Yvonne Brehmer, PhD
Gregoria Kalpouzos, PhD
Anna Rieckmann, PhD stud
University of Gothenburg
Linda Hassing, Assoc Prof
Valgeir Thorvaldsson, PhD
Anne Ingeborg Berg, PhD
Marcus Praetorius,
Peter Karlsson, PhD stud
Umeå University
Anna Neely Stigsdotter, PhD
Urban Ekman, PhD
Daniel Sjölie, PhD stud
Umeå University, Umeå
Per-Olof Sandman, Professor
Umeå University
Birgit Rasmussen, RN, PhD
David Edvardsson, RN, PhD
Karin Sjögren, RN, PhD stud
Karolinska Institutet
Louise Nygård, Professor
Karolinska Institutet, Stockholm
Lena Borell, Professor
Camilla Malinowsky, PhD
Eva Lindqvist, PhD
Sofia Wikström, PhD
Mandana Fallahpour, PhD
Lund University
Anna-Karin Edberg, Professor
Lund University
Anneli Orrung Wallin, PhD stud
University of Gothenburg
Helle Wijk, Assoc Professor
14
Primary Care, Health Economics,
Interactive training technology
Biomarkers (Imaging, CSF etc)
Genetics, Brain Bank
Karolinska Institutet, Stockholm
Anders Wimo, Professor
Karolinska Institutet, Stockholm
Linus Jönsson, MD, PhD
Anders Sköldunger, PhD stud
Britt-Marie Sjölund, PhD stud
Linköping University Hospital
Jan Marcusson, Professor
Linköping Univ Hospital
Anna Kvitting Segernäs, PhD stud
Maria Johansson, PhD stud
Umeå University
Helena Lindgren, PhD
Umeå University
Dipak Surie, PhD
Sahlgrenska Academy, Univ of
Gothenburg
Kaj Blennow, Professor
Sahlgrenska Academy, Univ of
Gothenburg
Henrik Zetterberg, MD, Professor
Annika Öhrfelt, PhD
Maria Bjerke, PhD
Pia Gudmundsson, PhD
Erik Portelius, PhD
Karolinska Institutet, Stockholm
Lars-Olof Wahlund, Professor
Karolinska Institutet, Stockholm
Agneta Nordberg, Professor
Dag Aarsland, Professor
Olof Lindberg, PhD
Eric Westman, PhD
Carlos Aguilar, PhD stud
Olga Voevodskaya, PhD stud
Aleksandra Lebedeva, PhD stud
Karolinska Institutet, Stockholm
Caroline Graff, MD, Professor
Karolinska Institutet, Stockholm
Lars Olson, Professor
Mimi Westerlund Olofsson, PhD
Andrea Carmine Belin, PhD
Dagmar Galter, PhD
Lina Rosvall, PhD
Huei-Hsin Chiang, PhD
Caroline Ran, PhD
Sandra Gellhaar, PhD
Vesna Jelic, PhD
Annica Rönnbäck, PhD
Charlotte Forsell, BMA
Lena Lilius, BMA
Marie Fallström, Brain Bank coord
Sahlgrenska Academy, Univ of
Gothenburg
Hans Nissbrandt, Professor
Sahlgrenska Academy, Univ of
Gothenburg
Elias Eriksson, Professor
Olle Bergman, PhD
Camilla Fardell, PhD stud
Umeå University
Peter M Andersen, Professor
Umeå University
Anna Birve, PhD
Angelica Nordin, PhD
Caroline Ingre, PhD stud
Helena Alstermark, technician
Lund University
Patrik Brundin, Professor
Sonia George, PhD
15
Linköping University
Martin Hallbeck, PhD
Lotta Agholme, PhD
Pre-clinical research,
Transgenic models
Karolinska Institutet, Stockholm
Lars Olson, Professor
Angel Cedazo-Minguez,
Assoc Professor
Ingemar Björkhem, Professor
Karolinska Institutet, Stockholm;
Marianne Schultzberg, Professor
Nils-Göran Larsson, Professor
Eirikur Benedikz, Assoc Prof
Lars Tjernberg, Assoc Prof
Erik Sundström, Assoc Prof
Helena Karlström, PhD
Andrea Carmine Belin, PhD
Anna Sandebring, PhD
Dagmar Galter, PhD
Susanne Frykman, PhD
Tobias Weber, PhD
Silvia Maioli, PhD stud
Jaime Ross, PhD stud
Mustafa Ismail, PhD stud
Torbjörn Persson, PhD stud
Anita Lövgren-Sandblom, BMA
Uppsala University
Lars Lannfelt, Professor
Martin Ingelsson, Assoc Prof
Dag Sehlin, PhD
Hedvig Welander, PhD
Lund University
Gunnar Gouras, Professor
Mathilde Faideau, PhD
Ethics
Karolinska Institutet, Stockholm
Erik Sundström, Assoc Professor
Maria Eriksdotter, Professor
Karolinska Institutet, Stockholm
Kevin Grimes, PhD
Sara Stormoen, PhD stud
Mette Bergman, PhD stud
16
Information dissemination
Knowledge dissemination and communication, both internal and external, is one of SBP’s
priorities. To this end SBP has, since October 2007, engaged a Communication Manager at
halftime to work close together with the Executive Group.
The overall goal is to make SBP’s position as a leading research network known to a wider
public in order to promote necessary investments in research to combat one of our fastest
growing public health problems; dementia.
Externally the aim is to reach relevant target groups such as other scientists, physicians’
clinics, patients, decision makers in society and industry as well as the general public.
Internally the aim is to facilitate and enhance communication and collaboration within the
network.
External and Internal
• The SBP website www.swedishbrainpower.se plays an important role in knowledge
dissemination, both externally and internally. The site presents the SBP and related
news to external target groups and to the public. The change in website technical
platform last year has enabled more focus on continuous update and news and the
statistics show a growing interest in the SBP website.
•
Statistics over SBP’s presence on Facebook www.facebook.com/SwedishBrainPower
and Twitter twitter.com/SwedBrainPower also show a growing, both internal and
external, interest.
•
Efforts to further increase the website’s accessibility and usability has been made
continuously by search optimizing and updating both content and technical
functions.
External
• Publication in scientific journals is the main channel for scientific knowledge
dissemination, both nationally and internationally. News about important
publications in major scientific journals is reported on the website in a popular form
along with links to the scientific articles.
•
The SBP scientists give lectures and present the SBP programme and the scientific
outcome at scientific conferences, as well as at public meetings and seminars, both
nationally and internationally, often in collaboration with patient associations.
•
The SBP-scientists are often interviewed in media and their appearances are
reproduced on the website.
17
•
A debate article has been published in the Swedish national newspaper “Svenska
Dagbladet” about the dementia threat to society. SBP-researchers have also
appeared in several specialty supplements to Swedish newspapers.
•
The existing portable roll ups and folders for presentation to target groups and public
have been supplemented with a leaflet in English giving details explaining how the
network is structured and works across both disciplinary and geographic boundaries.
Internal
• Every year a 2-day workshop is organized where all researchers in the network meet
and exchange experiences, ideas and results and where the young researchers in the
network present their cutting edge projects. This year, the workshop was held
October 10-11, 2013 at Vår Gård in Saltsjöbaden gathering 95 researchers
participating in SBP projects. We are especially happy that several of our Board
members participated at least partly in the meeting. An annual award of 5 000 SEK
each for best pedagogic oral and best pedagogic poster presentation is given out at
each workshop, aimed to be used for presenting the research project at an
international conference. This year Anna Lilja was awarded for her oral presentation
“Neurotrophic and neuroprotective actions of (-)- and (+)-phenserine, candidate
drugs for Alzheimer disease” and Annicka Hedman was awarded for her poster
presentation “Functioning over time in persons with MCI: Patterns of everyday
technology use and involvement in activities”.
•
A contact group of people from different research areas and sites has been formed to
provide the Communication Manager and the website with up-to-date information
from the various research groups in different parts of the country.
18
Research Budget Allocation
The grant from KAW Foundation for the SBP program during July 2010 – June 2015 (5 yrs) is
in total 100 MSEK. During year 8 (120701—130630), approx 20 MSEK has been allocated to
research projects in form of 50% salary support. Approx 3 MSEK has been used for
managerial and administrative costs, including part-time salary for managerial staff, website
and workshop, meetings and travels for all researchers involved in the program. See table
below.
COORDINATION CENTER
Salary cost
Salaries (Director, Co-Director, Adm coord)
Communikator
Board fees
SUM SALARIES
OTHERS COSTS
Rental
Meetings (board, leading groups, core groups)
Travels
Workshop
Recruitment announcement
Computer, softwares, web hotel
Office supplies
Other running costs
SUM OTHER COSTS
100701-110630 110701-120630 120701-130630
ÅR 8
ÅR 6
ÅR 7
1 441 848
830 833
1 404 828
355 857
76 517
402 724
300 000
210 000
300 000
2 097 705
1 117 350
2 107 552
116 000
18 162
113 354
328 605
116 000
38 101
114 172
279 327
24 331
16 114
10 598
17 845
296 691
30 494
6 031
44 659
657 305
13 681
1 597
15 027
577 905
SUM SALARY and OTHER COSTS
INDI 19%, 19.07% resp 15,38%
1 414 041
267 120
2 764 857
425 235
2 675 610
411 509
SUB TOTAL; costs taken centrally
1 681 161
3 190 092
3 087 119
ALLOCATED GRANTS FOR RESEARCH PROJECTS
201007—12 incl 19% INDI
201101—06 incl 19,07% INDI
201107—2013-06 incl 15,38% INDI
6 559 875
7 367 465
18 136 005
20 048 769
116 000
37 024
74 779
SUBTOTAL; ALLOCATED GRANTS
13 927 340
18 136 005
20 048 769
GRAND TOTAL COSTS
15 608 501
21 326 097
23 135 888
19
Below is summarized the allocation (%) of grants 2010-07—201306 (year 6-8) per university
and per project leader. No of Project Leaders per university: KI 19, Gbg 6, Malmö/Lund 4,
Umeå 4, Nordanstig 1, Linköping 2, Uppsala 1.
Matching funds
The SBP program only contributes with 50% of the salary for the given positions, even
though the researcher is expected to work full time for the project. That means that the unit
receiving SBP support contributes with the equal amount to cover for full salary. In addition,
they have to cover for all running costs needed to perform the project. By this, the recipients
of SBP grants contributes themselves with a total matching fund of approx 27 msek for the
63 positions including running costs.
The clinical trials performed at the three SBP clinics are estimated to render approx 20 msek
annually, mainly from international drug companies.
20
Swedish Brain Power
In FUTURE
Both nationally and internationally, Swedish Brain Power has become a well-known
trademark. Being a part of Swedish Brain Power is something all involved are very proud of.
The many recent publications in high impact journals and the high number of excellent PhD
examinations so far, is a proof of the scientific quality.
The Knut & Alice Wallenberg Foundation supports the SBP program for five years, ending
June 30, 2015. Since we are now entering into our fourth year, we are intensifying our work
trying to find support for primarily another five years. Our plans are to approach eg suitable
foundations and the host universities. To keep the network together requires to our mind not only a
small “network grant”, the criteria for allocation of funding to our researchers really have a great
impact on this why the optimal funding should include funding also for joint research projects.
We have appointed a small group of “younger” researchers to come up with new ideas and to take
main responsibility for this important task. As we have hard times to believe that we will not be able
to convince our stakeholders of the waste it would be to disrupt this successful program, we are
looking forward to the future with confidence.
For the Swedish Brain Power Program
Bengt Winblad
Director
Maria Eriksdotter
Co-Director
Gunilla Johansson
Coordinator
21
LIST OF RESEARCH PROJECTS
(In total 57 research projects)
22
CLINICAL PLATFORM (PI within brackets)
1. Multi-tracer PET studies for understanding of disease processes and development of early
diagnostic biomarkers (A Nordberg)
2. Imaging of astrocytes, fibrillar amyloid load and cerebral glucose metabolism in Tg mice with
APPswe mutation with µPET technique (A Nordberg)
3. Studies of neuroplasticity and functional neurogenesis in AD (A Nordberg)
4. A comparison between families with the C90RF72- and the SOD1 gene mutation in Swedish
families suffering from ALS or ALS/FTD (LO Wahlund, P Andersen)
5. Genetics of ALS/FTD and paraclinical studies (Fat dysmetabolisme, Q10, PET, MR-Imaging, NRF2)
(P Andersen)
6. Mevalonate pathway and cholesterol homeostasis in patients with different types of ALS and
ALS-FTD (I Björkhem, P Andersen)
7. Early diagnosis of AD (Tidig demensdiagnostik I Skåne, TIDIS) (L Minthon, O Hansson)
8. The Normal Material Study 2 (NoMaS 2) (K Nägga, L Minthon)
9. Cognitive impairment in elderly medical inpatients (L Minthon)
10. Neurochemical identification of incipient subcortical VaD and AD (A Wallin)
11. Functional and structural brain imaging (MRI) in normal aging, vascular and non-vascular MCI (A
Wallin)
12. Encapsulated cell bio-delivery of nerve growth factor (NGF) to Alzheimer disease patients (M
Eriksdotter)
13. Evaluation of Aβ oligomers/protofibrils as biomarkers for Alzheimer disease (L Lannfelt)
14. Genetic background and lifestyle-related factors in relation to risk of dementia and cognitive
decline (L Fratiglioni & I Skoog)
15. Longitudinal population-based studies in Sweden: Defining new clinical outcomes (L Fratiglioni)
16. Brain atrophy and cerebrovascular disease on CT in elderly population samples; risk factors,
secular changes and prognosis (I Skoog & LO Wahlund)
17. Individual differences in preclinical onset of dementia: What contributes to early/late onset of
cognitive decline? (L Bäckman & B Johansson)
18. Dopamine and cognitive plasticity across the adult life span (L Bäckman)
19. Can social and emotional well-being reduce the effects of AD and small vessel neuropathology
on neuropsychological functioning: Examining the socio-emotional reserve hypothesis in MCI
patients (B Johansson)
20. Interactive training techniques (L Nyberg)
21. Evaluation of emotional and cognitive impairment using VR technique (L Nyberg)
CARING / TECHNOLOGY PLATFORM
22. Exploring person-centred care in relation to health in people with dementia and staff in
residential aged care (PO Sandman)
23. Evidence-based environments (AK Edberg)
24. Detection of subtle and early signs of disability in terms of difficulties in everyday technology use
in older adults with MCI and AD (L Nygård)
25. The academic nursing home – a large scale intervention of the national guidelines for care of
dementia (L Borell)
26. Functional capacity and costs of care (A Wimo)
27. Dementia; costs for disease, drugs and diagnostics (A Wimo)
23
28. Cognitive testing and functional evaluation in primary care dementia investigations (J
Marcusson)
29. Providing tailored ICT-support to individuals with suspected or early dementia in their home and
to their health professionals (Helena Lindgren)
BASIC PLATFORM
30. Development of CSF biomarkers of synaptic degeneration in AD (K Blennow, J Gobom)
31. APP in CNS development and degeneration (K Blennow)
32. Lactate as a biomarker for aging and Alzheimer – a translational MRS study on mitochondrial
dysfunction (LO Wahlund)
33. Structural brain changes associated with depression and apathy in patients with AD (D Aarsland)
34. Genetic, neuropathological and clinical studies in FTLD (C Graff)
35. Clinical and experimental studies of FAD: a model for identifying prognostic and early diagnostic
markers of sporadic AD (C Graff)
36. Coordinator for a common neuropathological strategy in SBP projects (C Graff)
37. Prion-like propagation of Aβ- and tau-pathology in AD: translational studies in Tg mouse models
(P Brundin)
38. Defining Aβ/CTFβ induced synaptic changes in Alzheimer disease (G Gouras, L Tjernberg)
39. Disease-causing mutations in familial PD (H Nissbrandt)
40. Identification and modelling genetic factors in PD (A Carmine Belin)
41. Closing some of the gaps between genetic studies and pathology (D Galter)
42. Investigating the selective neuronal vulnerability in AD pathogenesis (L Tjernberg, A Sandebring)
43. The mitochondria theory of aging, mtDNA mutator mice and high brain lactate as early
biomarker of AD + translating ageing findings in mice to human brains, expression patterns of
LDH-A and B, and other genes… (L Olson)
44. LOTUS: A new regulator of brain plasticity; role in the formation of lasting memories (L Olson)
45. Three new ways to counteract disease phenotype in a genetic model of PD (L Olson)
46. APOE genotype and risk factors in AD; to understand the underlying mechanisms (A Cedazo
Minguez)
47. Modulation of gamma-secretase by APOE, a mechanistic explanation leading to sporadic AD (A
Cedazo Minguez)
48. Role of cholesterol metabolism and functions of oxysterols in healthy and AD brains (A Cedazo
Minguez & I Björkhem)
49. Role of the oxysterol 27-hydroxycholesterol in neurodegeneration (I Björkhem)
50. Inflammation as target for treatment of AD with special focus on the resolution phase (M
Schultzberg)
51. Biomarkers and memory in the transgenic AD rat (E Benedikz)
52. Role of the Aph-1 isoforms in the γ-secretase complex for selective processes of APP and Notch
(H Karlström)
53. Impact of gamma-secretase modulators and FAD-mutations on a wide range of gammasecretase substates (H Karlström, T Weber)
54. Neuronal cell cultures derived from induced pluripotent cells as a platform to study AD
mechanisms (E Sundström)
55. Investigation on cellular transmission for alpha-synuclein (M Hallbeck)
ETHICS
56. Medical decision making capacity in patients with compromised cognitive functions (E
Sundström)
57. To live with risk for Alzheimer disease (Maria Eriksdotter)
24
PUBLICATIONS
YEAR 8
(In total 150 publications;
81 within clinical platform, 20 within care/rehab platform and
49 within the basic research platform)
25
CLINICAL RESEARCH PLATFORM
(DIAGNOSTICS, THERAPEUTICS, CLINICAL TRIALS, EPIDEMIOLOGY, NEUROPSYCHOLOGY)
2013
Berg AI, Wallin A, Nordlund A, Johansson B. Living with stable MCI: experiences among 17 individuals
evaluated at a memory clinic. Aging Ment Health. 2013;17(3):293-9.
Billstedt E, Skoog I, Duberstein P, Hällström T, Andrén M, Björkelund C., Östling S, Waern, M. A 37
year prospective study of neuroticism and extroversion in women followed from mid-life to late life.
Acta Psychiatr Scand. 2013 Feb 19.
Billstedt E, Waern M, Duberstein P, Marlow T, Hellström T, Ostling S, Skoog I Secular changes in
personality: study on 75-year-olds examined in 1976-77 and 2005-2006. Int J Geriatr Psychiatry
2013;28:298-304.
Caracciolo B, Gatz M, Xu W, Marengoni A, Pedersen NL, Fratiglioni L. Relationship of subjective
cognitive impairment and cognitive impairment no dementia to chronic disease and multimorbidity
in a nation-wide twin study. J Alzheimers Dis. 2013 Jan 1;36(2):275-84.
Choo IH,Ni R, Schöll M et al. Combination of 18F-FDG PET and CSF biomarkers as a better predictor of
the progression to Alzheimer Disease in MCI patients. J Alzheimer´s Dis, 2013:33:929-939.
Daborg J, Holmgren S, Abramsson A, Andreasson U, Zetterberg M, Nilsson S, Minthon L, Skoog I,
Blennow K, Pekna M, Hanse E, Zetterberg H. Complement Gene Single Nucleotide Polymorphisms
and Biomarker Endophenotypes of Alzheimer's Disease. J Alzheimer’s Dis. 2013;35:51-7.
Eckerström C, Olsson E, Bjerke M, Malmgren H, Edman A, Wallin A, Nordlund A. A combination of
neuropsychological, neuroimaging, and cerebrospinal fluid markers predicts conversion from mild
cognitive impairment to dementia. J Alzheimer’s Dis. 2013 Jan 1;36(3):421-31
Eckerström M, Skoogh J, Rolstad S, Göthlin M, Steineck G, Johansson B, Wallin A. Sahlgrenska
Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q)--a research tool discriminating
between subjectively cognitively impaired patients and healthy controls. Int Psychogeriatr. 2013
Mar;25(3):420-30.
Edison P, Carter SF, Rinne JO et al. Comparison of MRI based and PET template based approaches in
the quantitative analysis of amyloid imaging with PIB-PET. Neuroimage 2013: 70:423-433.
Ferencz B, Laukka EJ, Lövdén M, Kalpouzos G, Keller L, Graff C, Wahlund LO, Fratiglioni L, Bäckman L.
The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory
in old age. Front Hum Neurosci. 2013 May 22;7:198.
Fredén Klenfeldt I, Karlsson B, Sigström R, Waern M, Östling S, Marlow T, Gustafson D, Skoog I.
Prevalence of Obsessive-compulsive Disorder in Relation to Depression and Cognition in an Elderly
Population. Am J Geriatr Psychiatry. 2013 Mar 13.
Guldberg-Kjär T, Sehlin S, Johansson B. ADHD symptoms across the lifespan in a population-based
Swedish sample aged 65 to 80. Int Psychogeriatr. 2013 Apr;25(4):667-75
26
Hange D, Mehlig K, Lauren L, Guo X, Bengtsson C, Skoog I, Björkelund C. Perceived mental stress in
women associated with psychosomatic symptoms, but not mortality: observations from the
Population Study of Women in Gothenburg. Int J Gen Med. 2013;6:307-15
Hjelm C, Broström A, Dahl A, Johansson B, Fredrikson M, Strömberg A. Factors Associated With
Increased Risk for Dementia in Individuals Age 80 Years or Older With Congestive Heart Failure. J
Cardiovasc Nurs. 2013 Jan 30. [Epub ahead of print]
Hörder H, Skoog I, Frändin K. Health-related quality of life in relation to walking habits and fitness: a
population-based study of 75-year-olds. Qual Life Res. 2013 Aug;22(6):1213-23.
Irz X, Fratiglioni L, Kuosmanen N, Mazzocchi M, Modugno L, Nocella G, Shakersain B, Traill WB, Xu W,
Zanello G. Sociodemographic determinants of diet quality of the EU elderly: a comparative analysis in
four countries. Public Health Nutr. 2013 May 9:1-13
Jokinen H, Schmidt R, Ropele S, Fazekas F, Gouw AA, Barkhof F, Scheltens P, Madureira S, Verdelho A,
Ferro JM, Wallin A, Poggesi A, Inzitari D, Pantoni L, Erkinjuntti T; LADIS Study Group. Diffusion
changes predict cognitive and functional outcome: the LADIS study. Ann Neurol. 2013 May;73(5):57683.
Johnell C, Religa D, Eriksdotter M. Dementia disorders and drug therapy: a nationwide study of over
7000 patients-data from SveDem. Ger Dem Cogn Disord 2013;35:239–248.
Jonsson Laukka E, Lövdén M, Herlitz A, Karlsson S, Ferencz B, Pantzar A, Keller L, Graff C, Fratiglioni L
& Bäckman L. Genetic effects on old-age cognitive functioning: A population-based study. Psychology
and Aging, 2013;28:262-274.
Kern S, Skoog I, Börjesson-Hanson A, Blennow K, Zetterberg H, Östling S, Kern J, Gudmundsson P,
Marlow T, Rosengren R, Waern M. Lower CSF Interleukin-6 predicts future depression in a
population-based sample of older women followed for 17 years. Brain Behav Immun. 2013
Aug;32:153-8.
Laukka EJ, Lövdén M, Herlitz A, Karlsson S, Ferencz B, Pantzar A, Keller L, Graff C, Fratiglioni L,
Bäckman L. Genetic effects on old-age cognitive functioning: a population-based study. Psychol
Aging. 2013 Mar;28(1):262-74.
Lövdén M, Jonsson Laukka E, Rieckmann A, Kalpouzos G, Li T-Q, Jonsson T, Wahlund LO, Fratiglioni L
& Bäckman L. The dimensionality of between-person differences in white-matter microstructure in
old age. Human Brain Mapping, 2013;34:1386-1398.
Magnusson K, Sehlin D, Syvänen S, Svedberg MM, Philipson O, Söderberg L, Tegerstedt K, Holmquist
M, Gellerfors P, Tolmachev V, Antoni G, Lannfelt L, Hall H, Nilsson LN. Specific Uptake of an Amyloidβ Protofibril-Binding Antibody-Tracer in AβPP Transgenic Mouse Brain. J Alzheimer’s Dis. 2013 Jan
1;37(1):29-40.
Marutle A, Gillberg PG, Bergfors A et al. 3H-deprenyl and 3H-PIB autoradiography show different
laminar distribution of astroglia and fibrillar ß-amyloid in Alzheimer brain. J Neuroinflammation
2013:10:90.
Mellqvist Fässberg M, Östling S, Börjesson-Hanson A, Skoog I, Waern M. Suicidal feelings in the
twilight of life: A cross-sectional population-based study of 97-year-olds. BMJ Open. 2013 Feb 1;3(2).
27
Morin J, Wiktorsson S, Marlow T, Olesen PJ, Skoog I, Waern M. Alcohol use disorder in elderly suicide
attempters: A controlled study. Am J Geriatr Psychiatry. 2013;21:196-203.
Ni R, Gillberg PG, Bergfors A et al. Amyloid tracers detect multiple binding sites in Alzheimer´s disease
brain tissue. Brain 2013: 136: 2217-2227.
Nordberg A, Carter SF, Rinne J et al. European multi-center PET study of fibrillar amyloid in
Alzheimer´s disease. Eur J Nucl Med Mol Imaging 2013: 40: 104-114
Olsson E, Klasson N, Berge J, Eckerström C, Edman A, Malmgren H, Wallin A. White Matter Lesion
Assessment in Patients with Cognitive Impairment and Healthy Controls: Reliability Comparisons
between Visual Rating, a Manual, and an Automatic Volumetrical MRI Method-The Gothenburg MCI
Study. J Aging Res. 2013;198471
Papenberg G, Bäckman L, Nagel IE, Nietfeld W, Schröder J, Bertram L, Heekeren HR, Lindenberger U
& Li S-C. (2013). Dopaminergic gene polymorphisms affect long-term forgetting in old age: Further
support for the magnification hypothesis. J Cognitive Neuroscience, 25, 571-579.
Pedersen NL, Christensen K, Dahl AK, Finkel D, Franz CE, Gatz M, Horwitz BN, Johansson B, Johnson
W, Kremen WS, Lyons MJ, Malmberg B, McGue M, Neiderhiser JM, Petersen I, Reynolds CA. IGEMS:
the consortium on Interplay of Genes and Environment across Multiple Studies. Twin Res Hum Genet.
2013 Feb;16(1):481-9.
Piccinin AM, Muniz-Terrera G, Clouston S, Reynolds CA, Thorvaldsson V, Deary IJ, Deeg DJ, Johansson
B, Mackinnon A, Spiro A 3rd, Starr JM, Skoog I, Hofer SM. Coordinated analysis of age, sex, and
education effects on change in MMSE scores. J Gerontol B Psychol Sci Soc Sci. 2013 May;68(3):37490.
Praetorius M, Thorvaldsson V, Hassing LB, Johansson B. Substantial effects of apolipoprotein E ε4 on
memory decline in very old age: longitudinal findings from a population-based sample. Neurobiol
Aging. 2013 Jul 12.
Prestia A, Caroli A, van der Flier V et al. Prediction of dementia in MCI patients based upon core
diagnostic markers for Alzheimer´s disease. Neurology 2013:80:1-9.
Qiu C, von Strauss E, Bäckman L, Winblad B, Fratiglioni L.Twenty-year changes in dementia
occurrence suggest decreasing incidence in central Stockholm, Sweden. Neurology. 2013 May
14;80(20):1888-94.
Reynolds CA, Zavala C, Gatz M, Vie L, Johansson B, Malmberg B, Ingelsson E, Prince JA, Pedersen NL.
Sortilin receptor 1 predicts longitudinal cognitive change. Neurobiol Aging. 2013 Jun;34(6):1710.e118.
Rolstad S, Berg AI, Bjerke M, Johansson B, Zetterberg H, Wallin A. Cerebrospinal fluid biomarkers
mirror rate of cognitive decline. J Alzheimer’s Dis. 2013 Jan 1;34(4):949-56.
Sjöberg L, Östling S, Waern M, Falk H, Skoog I. Secular changes in the relation between depression
and social factors. A study of two birth cohorts of Swedish septuagenarians followed for 5 years. J
Affect Disord. 2013 Sep 5;150(2):245-52.
28
Soveri A, Tallus J, Laine M, Nyberg L, Bäckman L, Hugdahl K, Tuomainen J, Westerhausen R &
Hämäläinen H. Modulation of auditory attention by training. Experimental Psychology, 2013;60:4452.
Wang HX, Jin Y, Hendrie HC, Liang C, Yang L, Cheng Y, Unverzagt FW, Ma F, Hall KS, Murrell JR, Li P,
Bian J, Pei JJ, Gao S. Late life leisure activities and risk of cognitive decline. J Gerontol A Biol Sci Med
Sci. 2013 Feb;68(2):205-13.
Wiberg P, Waern M, Billstedt E, Östling S, Skoog I. Secular trends in the prevalence of dementia and
depression in Swedish septugenarians 1976- 2006. Psychol Med. 2013 Mar 12:1-8.
Xu WL, Caracciolo B, Wang HX, Santoni G, Winblad B, Fratiglioni L. Accelerated progression from mild
cognitive impairment to dementia among APOE ε4ε4 carriers. J Alzheimer’s Dis. 2013;33(2):507-15.
Zhang H, Xu W, Dahl A, Xu Z, Wang HX, Qi X. Relation of socioeconomic status to impaired fasting
glucose and type 2 diabetes: findings based on a large population-based cross-sectional study in
Tianjin, China. Diabet Med. 2013 Feb 8.
Zhi X, Joas E, Waern M, Östling S, Börjesson-Hanson A, Skoog I. Prevalence of cardiovascular
disorders and risk factors in two 75-year-olds birth cohorts examined in 1976-77 and 2005-06. Aging
Clin Exp Res. 2013;25:377-83
Zimmermann-Viehoff F, Wang HX, Kirkeeid R, Schneiderma N, Erdur L, Dete H-C, K. Women’s
Exhaustion and Coronary Artery Atherosclerosis Progression. The Stockholm Female Coronary
Angiography Study. Psychosom Med. 2013 Jun;75(5):478-85.
2012
Andel R, Crowe M, Hahn EA, Mortimer JA, Pedersen NL, Fratiglioni L, Johansson B, Gatz M. Workrelated stress may increase the risk of vascular dementia. J Am Geriatr Soc. 2012 Jan;60(1):60-7.
Brehmer Y, Westerberg H & Bäckman L. Working-memory training in younger and older adults:
Training gains, transfer, and maintenance. Frontiers in Human Neuroscience, 2012;6:63.
Brown CL, Gibbons LE, Kennison RF, Robitaille A, Lindwall M, Mitchell MB, Shirk SD, Atri A, Cimino CR,
Benitez A, Macdonald SW, Zelinski EM, Willis SL, Schaie KW, Johansson B, Dixon RA, Mungas DM,
Hofer SM, Piccinin AM. Social activity and cognitive functioning over time: a coordinated analysis of
four longitudinal studies. J Aging Res. 2012; 287438.
Burzynska AZ, Nagel IE, Preuschhoff C, Gluth S, Bäckman L, Li S-C, Lindenberger U & Heekeren HR.
(2012). Cortical thickness is linked to executive functioning in adulthood and aging. Human Brain
Mapping, 33, 1607-1620.
Caracciolo B, Gatz M, Xu W, Pedersen NL, Fratiglioni L. Differential distribution of subjective and
objective cognitive impairment in the population: a nation-wide twin-study. J Alzheimer’s Dis 2012;
29: 393-403.
Cavallin L, Bronge L, Zhang Y, Oksengård AR, Wahlund LO, Fratiglioni L, Axelsson R. Comparison
between visual assessment of MTA and hippocampal volumes in an elderly, non-demented
population. Acta Radiol. 2012 Jun 1;53(5):573-9.
29
Clerici F, Caracciolo B, Cova I, Fusari Imperatori S, Maggiore L, Galimberti D, Scarpini E, Mariani C,
Fratiglioni L. Does vascular burden contribute to the progression of mild cognitive impairment to
dementia? Dement Geriatr Cogn Disord. 2012;34(3-4):235-43.
Eriksdotter-Jönhagen M, Linderoth B, Lindb G, Aladellie L, Almkvist O,Andreasen N, Blennow K,
Bogdanovic N, Jelic V, Kadir A, Nordberg A, Sundström E, Wahlund LO, Wall A, Wiberg M, Winblad B,
Seiger Å, Almqvist P, Wahlberg. Encapsulated cell biodelivery of NGF to the basal forebrain in
patients with Alzheimer´s disease. Dem Ger Cogn Disord. 2012;33:18-28.
Eriksdotter-Jönhagen M, Linderoth B, Lind G , Eyjolfsdottir H, Seiger Å, Almqvist P, Wahlberg L.
Intracerebral tillförsel av tillväxtfaktorn NGF med inkapslade celler hos patienter med Alzheimers
sjukdom. Neurologi 1: 15-22, 2012
Forsberg A, Engler H, Blomquist G et al. The use of PIB PET as a dual pathological and functional
biomarker in AD. Biochemica et Biophysica Acta 2012:1822: 380-385.
Jacobs AH, Taviatian B and the INMIND consortium. Noninvasive molecular imaging of
neuroinflammation. J Cereb Blood FLow Metab 2012: 32: 1393-1415.
Jonsson M, Skoog I, Marlow T, Mellqvist M, Waern M. Anxiety symptoms and suicidal feelings in a
population sample of non-demented 70-year-olds. Int Psychogeriatr. 2012;24:1865-71.
Jonsson Laukka E, MacDonald S W S, Fratiglioni L & Bäckman L. Preclinical cognitive trajectories differ
for Alzheimer's disease and vascular dementia. J Int Neuropsychol Society, 2012;18: 1-9.
Kadir A, Almkvist O, Forsberg A et al. Dynamic changes in PET amyloid and FGD imaging at different
stages of Alzheimer´s disease. Neurobiology of Aging 2012: 33: 198e-198e14.
Lak VW, Guo X, Skoog I. Secular trends in lung function and its relation to survival in Swedish 75-year
olds 1976-2006. Age Ageing. 2012;41:735-40.
Lindwall M, Cimino CR, Gibbons LE, Mitchell MB, Benitez A, Brown CL, Kennison RF, Shirk SD, Atri A,
Robitaille A, Macdonald SW, Zelinski EM, Willis SL, Schaie KW, Johansson B, Praetorius M, Dixon RA,
Mungas DM, Hofer SM, Piccinin AM. Dynamic associations of change in physical activity and change
in cognitive function: coordinated analyses of four longitudinal studies. J Aging Res. 2012;493598.
Lövdén M, Schaefer S, Noack H, Bodammer N, Kühn S, Heinze H-J, Düzel E, Bäckman L &
Lindenberger U. Spatial navigation training protects the hippocampus against age-related changes
during early and late adulthood. Neurobiology and Aging, 2012;33:620.
MacDonald SWS, Karlsson S, Rieckmann A & Bäckman L. (2012). Age-related increases in behavioral
variability: Relations to losses of dopamine D1 receptors. J Neuroscience, 32, 8186-8191.
Mangialasche F, Kivipelto M, Solomon A, Fratiglioni L. Dementia prevention: current epidemiological
evidence and future perspective. Alzheimers Res Ther. 2012 Feb 13;4(1):6
Mitchell MB, Cimino CR, Benitez A, Brown CL, Gibbons LE, Kennison RF, Shirk SD, Atri A, Robitaille A,
Macdonald SW, Lindwall M, Zelinski EM, Willis SL, Schaie KW, Johansson B, Dixon RA, Mungas DM,
Hofer SM, Piccinin AM. Cognitively Stimulating Activities: Effects on Cognition across Four Studies
with up to 21 Years of Longitudinal Data. J Aging Res. 2012;461592. Epub 2012 Sep 13.
Nilsson J, Ostling S, Waern M, Karlsson B, Sigström R, Guo X, Skoog I.. The 1-month prevalence of
Generalized Anxiety Disorder according to DSM-IV, DSM-V and ICD-10 among non-demented 75year-olds in Gothenburg, Sweden. Am J Geriatr Psychiatry. 2012;20:963-72.
30
Nyberg L, Lövdén M, Riklund K, Lindenberger U & Bäckman L. Memory aging and brain maintenance.
Trends in Cognitive Sciences, 2012;6:292-305.
Paillard-Borg S, Fratiglioni L, Xu W, Winblad B, Wang HX. An active lifestyle postpones dementia
onset by more than one year in very old adults. J Alzheimer’s Dis. 2012;31(4):835-42.
Richard E, Andrieu S, Solomon A, Mangialasche F, Ahtiluoto S, Moll van Charante EP, Coley N,
Fratiglioni L, Neely AS, Vellas B, van Gool WA, Kivipelto M. Methodological challenges in designing
dementia prevention trials - the European Dementia Prevention Initiative (EDPI). J Neurol Sci. 2012
Nov 15;322(1-2):64-70.
Rieckmann A, Karlsson S, Fischer H & Bäckman L. Increased bilateral frontal connectivity in younger
adults under the influence of a dopamine D1 receptor antagonist. J Neuroscience 2012;32: 1706717072.
Rizzuto D, Orsini N, Qiu C, Wang HX, Fratiglioni L. Lifestyle, social factors, and survival after age 75:
population based study. BMJ. 2012 Aug 29;345:e5568
Robitaille A, Muniz G, Piccinin AM, Johansson B, Hofer SM. Multivariate Longitudinal Modeling of
Cognitive Aging: Associations Among Change and Variation in Processing Speed and Visuospatial
Ability. GeroPsych (Bern). 2012;25(1):15-24.
Rolstad S, Berg AI, Zetterberg H, Johansson B, Wallin A. All cognitive systems but speed and
visuospatial functions reduce the effect of CSF pathology on other systems. Curr Alzheimer Res. 2012
Nov;9(9):1043-9.
Rydwik E, Welmer AK, Kåreholt I, Angleman S, Fratiglioni L, Wang HX. Adherence to physical exercise
recommendations in people over 65--The SNAC-Kungsholmen study. Eur J Public Health. 2012 Oct
31.
Sehlin D, Englund H, Simu B, Karlsson M, Ingelsson M, Nikolajeff F, Lannfelt L, Pettersson FE. Large
aggregates are the major soluble Aβ species in AD brain fractionated with density gradient
ultracentrifugation. PLoS One. 2012;7(2):e32014
Torisson G, Minthon L, Stavenow L, Londos E. Cognitive impairment is undetected in medical
inpatients: a study of mortality and recognition amongst healthcare professionals. BMC Geriatr.
2012;12:47.
Wahlberg LU, Lind G, Almqvist PM, Kusk P, Tornøe J, Juliusson B, Söderman M, Selldén E, Seiger, Å,
Eriksdotter-Jönhagen M. Linderoth, B,.Targeted therapy of NGF in Alzheimer’s disease with EC
Biodelivery™ – A technology platform for restorative neurosurgery, J Neurosurg. 2012;117:340- 347.
Welmer AK, Kåreholt I, Angleman S, Rydwik E, Fratiglioni L. Can chronic multimorbidity explain the
age-related differences in strength, speed and balance in older adults? Aging Clin Exp Res. 2012
Oct;24(5):480-9.
Wenger E, Schaefer S, Noack H, Kühn S, Mårtensson J, Heinze H-J, Düzel E, Bäckman L, Lindenberger
U & Lövdén M. Cortical thickness changes following spatial navigation training in adulthood and
aging. Neuroimage, 2012;59: 3389-339.
Villemagne V, Klunk WE, Mathis CA et L: Aß imaging: feasible, pertinent, and vital to progress in
Alzheimer´s disease. Eur J Jucl Med Mol Imaging 2012: 39: 209-2
31
Xu W, Xu Z, Jia J, Xie Y, Wang HX, Qi X. Detection of Prediabetes and Undiagnosed Type 2 Diabetes: A
Large Population-based Study. Can J Diabetes. 2012;36(3):108-13.
CARE/CARING RESEARCH PLATFORM
(CARE, REHABILITATION, TECHNOLOGY, PRIMARY CARE, HEALTH ECONOMY)
2013
Kvitting AS, Wimo A, Johansson MM, Marcusson J. A quick test of cognitive speed (AQT): usefulness
in dementia evaluations in primary care. Scand J Prim Health Care. 2013 Mar;31(1):13-9.
Lindgren H, Nilsson I. Towards User-Authored Agent Dialogues for Assessment in Personalised
Ambient Assisted Living. Int. J. of Web Engineering and Technology, 2013;8(2):154-176.
Lindgren H. Sociotechnical Systems as Innovation Systems in the Medical and Health Domain. Stud
Health Technol Inform 2013;194:35-40.
Orrung Wallin A, Edberg AK, Beck I, & Jakobsson U. Psychometric properties concerning four
instruments measuring job satisfaction, strain and stress of conscience in a residential care context.
Archives of Gerontology and Geriatrics, 2013;57(2): 162-171.
Orrung Wallin, A., Jakobsson, U. & Edberg, A-K. (2013) Job strain and stress of conscience among
nurse assistants working in residential care. J Nursing Management, E-pub ahead of print.
Sköldunger A, Wimo A, Johnell K. Net costs of dementia in Sweden - an incidence based 10 year
simulation study. Curr Alzheimer Res. 2013 Feb;10(2):207-16.
Surie D, Lindgren H, Qureshi A. Kitchen AS-A-PAL: Exploring Smart Objects as Containers, Surfaces
and Actuators. In: Ambient Intelligence-Software and Applications, pp. 171–178. Springer, 2013.
Tallberg I-M, Stormoen S, Almkvist O, Eriksdotter M, Sundström E. Investigating medical decisionmaking capacity in patients with cognitive impairment using a protocol based on linguistic features.
Scand J Psychol. 2013;54:386-92, 2013.
2012
Boman I-L, Rosenberg L, Lundberg S & Nygård L. A first step in designing a videophone for people
with dementia: identification of the users’ potentials and the requirements on the communication
technology. Disability and Rehabilitation: Assistive Technology, 2012;7(5):356-363.
Borell L, Nygård L, Asaba E, Gustavsson A & Hemmingsson H. Qualitative Approaches in Occupational
Therapy Research. Scandinavian J Occupational Therapy, 2012;9,(oct): 521-529.
Lindgren H, Winnberg PJ, Yan C. Collaborative Development of Knowledge-Based Support Systems: A
Case Study. Stud Health Technol Inform 2012;180:1111-1113.
Malinowsky C, Almkvist O, Nygård L & Kottorp A. Individual variability and environmental
characteristics influence older adults’ abilities to manage everyday technology. International
Psychogeriatrics, 2012; 24:484-495.
32
Nieves JC, Surie D, Lindgren H. Modeling Actions Based on a Situative Space Model for Recognizing
Human Activities. In: A. Ramsay and G. Agre (Eds.): AIMSA 2012, LNAI 7557, pp. 266-275.
Nygård L, Pantzar M, Uppgard B & Kottorp A. Detection of disability in older adults with MCI or
Alzheimer’s disease through assessment of perceived difficulty in using everyday technology. Aging
and Mental Health, 2012;16(3-4):361-371.
Orrung Wallin, A., Jakobsson, U., Edberg, A-K. Job-satisfaction and associated variables among nurse
assistants working in residential care. International Psychogeriatrics, 2012;24(12): 1904-1918.
Sandman PO, Edvardsson D. Existential outcomes of person-centred care – how can such be
measured, achieved, implemented and disseminated. The Gerontologist 2012;52 (s1), 451.
Sjögren K, Petersson L, Sandman P, Edvardsson D. Everyday activities are associated with higher
resident quality of life. The Gerontologist 52 (s1), 451.
Sjögren K, Lindqvist M, Zingmark K, Sandman PO, Edvardsson D. Person-Centredness and its
association with resident well-being in dementia care units. Journal of Advanced Nursing
Sjögren K, Sandman PO, Zingmark K, Edvardsson D. Psychometric evaluation of the Swedish version
of the Person-centred Care Assessment Tool (P-CAT). International Psychogeriatrics 2012; 24, 406415.
Sköldunger A, Johnell K, Winblad B, Wimo A. Mortality and treatment costs have a great impact on
the cost-effectiveness of disease modifying treatment in Alzheimer's disease--a simulation study. Int J
Geriatr Psychiatry. 2012 Nov;27(11):1112-7.
BASIC RESEARCH PLATFORM;
(EXPERIMENTAL RESEARCH, GENETICS, ANIMAL MODELS)
2013
Akimoto C, Linder J, Nilsson A-C, Forsgren L, Alstermark H, Birve A, Andersen PM. No GGGGCC
hexanucleotide repeat expansion in C9orf72 in patients with Parkinson’s Disease or Parkinsonisme.
Amyotroph Lateral Scler Frontotemporal Degener 2013;14:26-29.
Brinkmalm G, Brinkmalm A, Bourgeois P, Persson R, Hansson O, Portelius E, Mercken M, Andreasson
U, Parent S, Lipari F, Öhrfelt A, Bjerke M, Minthon L, Zetterberg H, Blennow K, Nutu M. Soluble
Amyloid Precursor Protein α and β in CSF in Alzheimer's Disease. Brain Res 2013;1513:117-126.
Chiang HH, Forsell C, Lilius L, Öijerstedt L, Thordardottir S, Shanmugarajan K, Westerlund M,
Nennesmo I, Thonberg H, Graff C. Novel progranulin mutations with reduced serum-progranulin
levels in frontotemporal dementia. Eur J Human Genetics, 2013;Mar 6.
Czell D, Andersen PM, Neuwirth C, Morita M, Weber M. Progressive aphasia as the presenting
symptom in a patient with amyotrophic lateral sclerosis with a novel mutation in the OPTN gene.
Amyotroph Lateral Scler Frontotemporal Degener 2013;14:138-140.
33
Czell D, Andersen PM, Morita M, Neuwirth C, Perren F, Weber M. Phenotypes in Swiss patients with
familial ALS carrying TARDBP mutations. Neurodegener Dis 2013, E-pub Jan 10.
Dillman AA, Hauser DN, Gibbs JR, Nalls MA, McCoy MK, Rudenko IN, Galter D, Cookson MR. mRNA
expression, splicing and editing in the embryonic and adult mouse cerebral cortex. Nature Neurosci.
2013 Apr;16(4):499-506
Eschbach J, Schwalenstöcker B, Soyal S, Bayer H, Wiesner D, Akimoto C, Nilsson A-C, Birve A, Meyer
T, Dupuis L, Danzer K, Andersen PM, Witting A, Ludolph AC, Patsch W, Weydt P. PGC-1α is a sexdependent modifier of human and experimental ALS. Hum Mol Genet 2013;22:3477-84.
Hedskog et al. Modulation of the ER-mitochondria interface in Alzheimer disease brain and related
models. Proc Natl Acad Sci U S A. 2013 Apr 25
Hedskog et al. Biochemical studies of poly-T variants in the Alzheimer's disease associated TOMM40
gene. J Alzheimer’s Dis. 2013;31(3):527-36
Hedskog L, Pinho CM, Filadi R, Rönnbäck A, Hertwig L, Wiehager B, Larssen P, Gellhaar S, Sandebring
A, Westerlund M, Graff C, Winblad B, Galter D, Behbahani H, Pizzo P, Glaser E, Ankarcrona M.
Modulation of the endoplasmic reticulum-mitochondria interface in Alzheimer's disease and related
models. Proc Natl Acad Sci U S A. 2013 May 7;110(19):7916-21.
Hjorth E, Vedin I, Palmblad J, Cederholm T, Freund-Levi Y, Faxen Irving G, Wahlund L-O, Basun H,
Eriksdotter M, Schultzberg M. Omega-3 fatty acids enhance phagocytosis of Alzheimer’s diseaserelated amyloid-β42 by human microglia and decrease inflammatory markers. J Alz Dis 2013;35:697–
713
Ibáñez C, Simó C, Barupal DK, Fiehn O, Kivipelto M, Cedazo-Mínguez A, Cifuentes A. A new
metabolomic workflow for early detection of Alzheimer's disease. J Chromatogr A. 2013 Aug
9;1302:65-71
Ingre C, Landers JE, Rizik N, Akimoto C, Birve A, Keagle PJ, Piotrowska K, Press R, Andersen PM,
Ludolph AC, Weishaupt JH. A novel phosphorylation site mutation in Profilin 1 revealed in a large
screen of US, Nordic and German ALS/FTLD cohorts. Neurobiol Aging 2013;34:1708.e1-6
Ingre C, Pinto S, Birve A, Press R, Danielsson O, de Carvalho M, Guðmundsson G, Andersen PM. No
association between VAPB mutations and familial or sporadic ALS in Sweden, Portugal and Iceland. ALS
and FTD. Amyotroph Lateral Scler Frontotemporal Degener 2013 (epub August 23)
Karlsson T, Karlén A, Olson L, Josephson A. Neuronal over-expression of Nogo Receptor 1 in
APPswe/PSEN1(dE9) mice impairs spatial cognition tasks without influencing plaque formation. J
Alzheimer’s Dis 33, 145–155, 2013
Karlsson TE, Koczy J, Brené S, Olson L, Josephson A. Differential concerted activity induced regulation
of Nogo receptors (1-3), LOTUS and Nogo mRNA in mouse brain. Plos One, 8, e60892, 2013
Olson L. Combinatory treatments needed for spinal cord injury. July 2, 2013 (Epub ahead of print) - A
review that includes a discussion to the Nogo signaling system for CNS plasticity. Exp. Neurol.
Paus M, Kohl Z, Ben Abdallah NM, Galter D, Gillardon F, Winkler J. Enhanced dendritogenesis and
axogenesis in hippocampal neuroblasts of LRRK2 knockout mice. Brain Res. 2013 Feb 25; 1497: 85100.
34
Pihlstrøm L, Axelsson G, Bjørnarå KA, Dizdar N, Fardell C, Forsgren L, Holmberg B, Larsen JP, Linder J,
Nissbrandt H, Tysnes OB, Ohman E, Dietrichs E, Toft M. Supportive evidence for 11 loci from genomewide association studies in Parkinson's disease. Neurobiol Aging, 34, 1708.e7-13, 2013.
Ran C, Willows T, Sydow O, Johansson A, Söderkvist P, Dizdar N, Ahmadi A, Olson L, Belin AC. The
HLA-DRA variation rs3129882 is not associated with Parkinson’s Disease in Sweden. Parkinsonism
Relat Disord. 2013 Jul;19(7):701-2
Ross JM, Stewart JB, Hagström E, Brene S, Mourier A, Coppotelli G, Freyer C, Lagouge M, Hoffer BJ,
Olson L, Larsson NG. Germline mitochondrial DNA mutations aggravate ageing and can impair brain
development. Nature. 2013 Aug 21.
Sandebring A, Welander H, Winblad B, Graff C, Tjernberg Lars O. The pathogenic Aβ43 is enriched in
familial and sporadic Alzheimer disease. PLoS One. 2013;8(2)
Sarlus H, Wang X, Cedazo-Minguez A, Schultzberg M, Oprica M. Chronic airway-induced allergy in
mice modifies gene expression in the brain toward insulin resistance and inflammatory responses. J
Neuroinflam2013;10:99.
Schedin-Weiss S, Inoue M, Teranishi Y, Yamamoto NG, Karlström H, Winblad B, Tjernberg LO.
Visualizing active enzyme complexes using a photoreactive inhibitor for proximity ligation-application on γ-secretase. PLoS One. 2013 May 24;8(5):e63962.
Smith BN, Newhouse S, Vance C, Lee Y, Weale ME, Topp S, Millar J, Johnson L, Troakes C, Hortobagyi
T, Al-Sarraj S, Rogelj B, Powell J, Lupton M, Lovestone S, Sapp P, Nestor PS, Schelhaas, Silani V, Gelera
C, Van den Berg L, Veldink J, van Damme P, Robberecht W, de Jong V, Shaw PJ, Kirby J, Paul H,
Morrison KE, Bass, Andersen PM, Landers J, Brown RH, Al-Chalabi A, Shaw CE. The C9ORF72
expansion mutation is derived from a single founder in European ALS/FTD patients and is highly
unstable. Eur J Hum Genet 2013;21:102-108.
Van der Zee et al. A Pan-European study of the C9orf72 repeat associated with FTLD: geographic
prevalence, genomic instability and intermediate repeats. Human Mutation, 2013;34:363-73.
Waibel S, Neumann M, Rosenbohm A, Birve A, Volk A, Weishaupt JH, Meyer T, Müller U, Andersen PM,
Ludolph AC. Truncating mutations in FUS/TLS give rise to a more aggressive ALS-phenotype than
missense mutations: A clinico-genetic study in Germany. Eur J Neurol 2013;20:540-546.
Wang K, Ju X, Wei L, Zuo X, Tia Y, Xie F, Hu P, Zhu C, Yu F, Meng Y, Wang H, Zhang F, Ma H, Ye R,
Cheng H, Du J, Dong W, Zhou S, Wang C, Wang Y, Wang J, Chen X, Sun Z, Zhou N, Jiang Y, Liu X, Li X,
Zhang N, Liu N, Guan Y, Han Y, Han Y, Lv X, Fu Y, Yu H, Xi C, Xie D, Zhao O, Xie P, Wang X, Zhang Z,
Shen L, Cui Y, Yin X, Cheng H, Liang B, Zheng X, Lee TMC, Chen G, Zhou F, Veldink JH, Robberecht W,
Landers J, Andersen PM, Al-Chalabi A, Shaw C, Liu C, Tang B, Xiao S, Robertson J, Fengyu Zhang F, van
den Berg LH, Sun L, Liu J, Deng M, Yang S, Zhang X. Genome-wide association analyses in Chinese Han
identify two new susceptibility loci for amyotrophic lateral sclerosis. Nat Genet 2013;45:697-700.
Weishaupt JH, Waibel S, Birve A, Volk AE, Mayer B, Meyer T, Ludolph AC, Andersen PM. A novel
optineurin truncating mutation and three glaucoma-associated missense variants in patients with
familial amyotrophic lateral sclerosis in Germany. Neurobiol Aging 2013;34:1516
35
Zheng L, Calvo-Garrido J, Hallbeck M, Hultenby K, Marcusson J, Cedazo-Minguez A, TermanA
Intracellular Localization of Amyloid-β Peptide in SH-SY5Y Neuroblastoma Cells. J Alzheimers Dis.
2013 Jul 23.
2012
Belin AC, Ran C, Anvret A, Paddock S, Westerlund, Håkansson A, Nissbrandt H, Söderkvist P, Dizdar N,
Ahmadi A, Anvret M, Willows T, Sydow O, Galter D. Association of a protective paraoxonase 1 (PON1)
polymorphism in Parkinson’s disease. Neurosci Lett. 2012 Jul 26;522(1):30-5.
Borgegård T, Gustavsson S, Nilsson C, Parpal S, Klintenberg R, Berg AL, Rosqvist S, Serneels L,
Svensson S, Olsson F, Jin S, Yan H, Wanngren J, Jureus A, Ridderstad-Wollberg A, Wollberg P,
Stockling K, Karlström H, Malmberg A, Lund J, Arvidsson PI, De Strooper B, Lendahl U, Lundkvist.
J.Alzheimer's disease: presenilin 2-sparing γ-secretase inhibition is a tolerable Aβ peptide-lowering
strategy. J Neurosci. 2012 Nov 28;32(48):17297-305.
Carmine Belin A, Ran C, Anvret A, Paddock S, Westerlund M, Håkansson A, Nissbrandt H, Söderkvist P,
Dizdar N, Ahmad Ahmadi A, Anvret M, Willows T, Sydow O, Galter D. Association of a protective
paraoxonase 1 (PON1) polymorphism in Parkinson’s disease. Neuroscience Lett, 522, 30-35, 2012.
Corcia P, Ingre C, Blasco H, Press R, Praline J, Antar C, Veyrat C, Guettard YO, Camu W, Andersen PM,
Andres C, Vourc’h P. Homozygous SMN2 deletion is a protective factor in the Swedish ALS
population. Eur J Hum Genet 2012;20:588-91.
Fourgeux C, Dugas B, Richard F, Björkhem I, Acar N, Bron AM, Korobelnik JF, Levezei N, Zerbib J,
Puche N, Creuzot-Garcher CP, Bretillon L Single nucleotide polymorphism in the cholesterol 24Shydroxylase (CYP46A1) gene and its association with CFH and LOC387715 gene polymorphisms in
age-related macular degeneration. Invest Ophtalmol Vis Sci. 53 (2012) 7026-7033
Gil-Bea F, Akterin S, Persson T, Mateos L, Sandebring A, Avila-Cariño J, Gutierrez-Rodriguez A,
Sundström E, Holmgren A, Winblad B, Cedazo-Minguez A. Thioredoxin-80 is a product of alphasecretase cleavage that inhibits amyloid-beta aggregation and is decreased in Alzheimer's disease
brain. EMBO Mol Med. 2012 Oct;4(10):1097-111.
Ibáñez C, Simó C, Martín-Álvarez PJ, Kivipelto M, Winblad B, Cedazo-Mínguez A, Cifuentes A. Toward
a predictive model of Alzheimer's disease progression using capillary electrophoresis-mass
spectrometry metabolomics. Anal Chem. 2012 Oct 16;84(20):8532-40.
Hjorth E, Freund-Levi Y. Immunomodulation of microglia by docosahexaenoic acid and
eicosapentaenoic acid. Curr Opin Clin Nutr Metab Care 2012;15:134-143
Kacem I, Funalot B, Torny F, Lautrette G, Andersen PM, Couratier P. Early-onset parkinsonism
associated with an intronic SOD1 mutation. ALS 2012;13:315-317.
Katz JS, Katzberg HD, Woolley SC, Marklund SL, Andersen PM. Fronto-temporal dementia with
Aphasia and later Amyotrophic Lateral Sclerosis in a Patient with the I113T SOD1 Gene Mutation.
Amyotroph Lateral Scler 2012;13:567-9.
Lee SM, Sterky FH, Mourier A, Terzioglu M, Paganelli A, Cullheim S, Olson L, Larsson NG. Mitofusin 2
is necessary for striatal axonal projections of midbrain dopamine neurons. Hum Mol Genet, 21, 48274835, 2012
36
Sarlus H, Olgart Höglund C, Karshikoff B, Wang X, Lekander M, Schultzberg M, Oprica M (2012)
Allergy influences the inflammatory status of the brain and enhances tau phosphorylation. J Cell Mol
Med 2012 Feb 22.
Sharma M, Ioannidis JP, Aasly JO, Annesi G, Brice A, Van Broeckhoven C, Bertram L, Bozi M, Crosiers
D, Clarke C, Facheris M, Farrer M, Garraux G, Gispert S, Auburger G, Vilariño-Güell C, Hadjigeorgiou
GM, Hicks AA, Hattori N, Jeon B, Lesage S, Lill CM, Lin JJ, Lynch T, Lichtner P, Lang AE, Mok V,
Jasinska-Myga B, Mellick GD, Morrison KE, Opala G, Pramstaller PP, Pichler I, Park SS, Quattrone A,
Rogaeva E, Ross OA, Stefanis L, Stockton JD, Satake W, Silburn PA, Theuns J, Tan EK, Toda T,
Tomiyama H, Uitti RJ, Wirdefeldt K, Wszolek Z, Xiromerisiou G, Yueh KC, Zhao Y, Gasser T,
Maraganore D, Krüger R; *GEO-PD Consortium. Large-scale replication and heterogeneity in
Parkinson disease genetic loci. Neurology. 2012 Aug 14;79(7):659-67 *Global Site Principal
investigator of GEO-PD in Sweden.
Sterky FH, Hoffman AF, Milenkovic D, Bao B, Paganelli A, Edgar D, Wibom R, Lupica CR, Olson L,
Larsson NG. Altered dopamine metabolism and increased vulnerability to MPTP in mice with partial
deficiency of mitochondrial complex I in dopamine neurons. Hum Mol Genet 2012;21:1078-1089.
Synofzik M, Rochi D, Keskin I, Basak AN, Wilhelm C, Gobbi C, Birve A, Biskup S, Zecca C, FernandezSantiago R, Kaugesaar T, Schöls L, Marklund SL, Andersen PM. Mutant Superoxide Dismutase-1
Indistinguishable from Wild Type Causes ALS. Hum Mol Genet 2012;21:3568-3574.
van Hoecke A, Schoonaert L, Lemmens R, Timmers M, Staats KA, Laird AS, Peeters E, Philips T, Goris
A, Dubois B, Andersen PM, Al-Chalabi A, Thijs V, Turnley AM, van Vught PW, Veldink JH, Van Den
Bosch L, Gonzalez-Perez P, Van Damme P, Brown Jr RH, van den Berg LH, Robberecht W. EPHA4 is a
disease modifier of amyotrophic lateral sclerosis in animal models and in humans. Nat Med
2012;18:1418-1422.
Wanngren J, Ottervald J, Parpal S, Portelius E, Strömberg K, Borgegård T, Klintenberg R, Juréus A,
Blomqvist J, Blennow K, Zetterberg H, Lundkvist J, Rosqvist S, Karlström H. Second generation γsecretase modulators exhibit different modulation of Notch β and Aβ production. J Biol Chem. 2012
Sep 21;287(39):32640-50.
Zhang YJ, Granholm AC, Shan L, Diaz O, Malik N, Olson L, Huh K, Hoffer BJ, Lupica CR, Hoffman AF,
Bäckman CM. Lack of PTEN enhances survival, neurite outgrowth and function of dopamine neuron
grafts to MitoPark mice. Brain 2012;135:2736-2749.
Zheng L, Cedazo-Minguez A, Hallbeck M, Jerhammar F, Marcusson J, Terman A. Intracellular
distribution of amyloid beta peptide and its relationship to the lysosomal system. Transl
Neurodegener. 2012 Sep 26;1(1):19.
37