Brain Matters 2016
The newsletter from Queen Square Brain Bank
for Neurological Disorders
Welcome
Professor Tom Warner,
Clinical Director of Queen Square Brain Bank
welcomes you to the eleventh edition
of Brain Matters.
“As the Queen Square Brain Bank (QSBB) entered its fourth decade we said goodbye to one of its most loyal staff.
Susan Stoneham, featured in Brain Matters 2015, retired in January after twenty five years working as administrator to QSBB
and The Sara Koe PSP Research Centre. Over the years, many donors, their relatives and friends will have spoken to or even
met Susan. Always calm, courteous and charming, she worked tirelessly to orchestrate the “front of house” of QSBB ensuring
its smooth running and acting as its public face. She had unique skills and her empathetic manner and organisation will
be greatly missed by her friends, colleagues and, most importantly, those on the brain donor scheme and their families.
Finding a successor to Susan was going to be a difficult task and I am pleased to introduce Lynn Haddon who was appointed
from a very competitive field of candidates. Lynn brings many qualities and skills from previous experience as administrator to a
large academic department at Queen Mary University of London and from her work with patients and their relatives at The Barts
Cancer Institute. She also has in depth IT experience which will be invaluable as we update our computer systems and database.
Over the last year there has been increasing political and media coverage of dementia and its effect on the ageing population.
As with other neurodegenerative disorders such as progressive supranuclear palsy and multiple system atrophy, the study of
brain tissue plays a critical role in understanding how the brain cells involved die, and in identifying potential ways this can
be treated. At QSBB we continue to work closely with the Dementia Research Centre at the National Hospital for Neurology
and Neurosurgery, led by Professor Nick Fox, to encourage donation from well-studied patients with the commonest forms of
dementia, familial Alzheimer’s disease and frontotemporal dementia. This productive collaboration complements our ongoing
research programme investigating the causes of Parkinson’s disease and atypical parkinsonism as the most prevalent forms
of neurodegeneration.
Finally, I would like to emphasise that the world class reputation of QSBB
is entirely based on the selfless generosity of brain donors and their families,
to whom we are very grateful.”
Lynn Haddon – photo courtesy of PSPA
Research Updates
This new information could be key to developing a strategy
to alter the course of progression and ultimately to stop the
disease in its tracks.”
Image (left) shows Christina collecting samples of tissue
to be analysed
Professor Janice Holton, Neuropathology Director and
Dr Aoife Kiely, Research Fellow continue their studies in
multiple system atrophy, funded by the Multiple System
Atrophy Trust and MSA Coalition:
Ms Christina Murray, PhD student, and Dr Sonia Gandhi,
Wellcome Trust Fellow and Consultant Neurologist give
an update on their study, funded by Parkinson’s UK:
“The aim of our project is to investigate the way in which
Parkinson’s disease (PD) begins and progresses in the brain.
As the disease advances, the brain pathology increases in
severity and spreads to affect many areas. We wanted to
explore the earliest pathological changes that occur using a
technique called proteomics, which is the investigation of all
the proteins present in a cell or brain tissue at any one time.
Proteins are the basic building blocks of all cells and if
defective can disturb normal functioning. The brain, a
complex organ contains thousands of different proteins and
our proteomics technique provides a snapshot of several of
these, including defective ones.
We analysed brain samples donated from individuals who had
early signs of PD during life. At this stage only certain brain
areas are affected with Lewy bodies, the pathological hallmark
of PD, made up of a protein called alpha-synuclein. Other
regions are spared until later in the disease development.
Previous studies show that mitochondria, which produce
energy for the cell and are crucial for cell function, become
dysfunctional in Parkinson’s disease. However, it is not
known whether abnormal mitochondria function precedes
the pathology.
Our findings imply that this could in fact be the case.
Mitochondrial proteins are changing in brain areas in PD
that do not yet have pathology but would at a later stage,
suggesting that mitochondrial dysfunction appears to be
one of the first processes to be affected.
“The multiple system atrophy (MSA) research group at QSBB
is utilising diverse methods to understand the cause of MSA.
So far our work has shown that the immune system of the
brain may not be functioning properly in this disease resulting
in over activity known as neuroinflammation. We used state
of the art technology to look closely at a large number of
indicators of inflammation in brain regions typically affected.
This has given us a unique opportunity to find several new
targets for future studies that may be valuable in developing
treatments for the disease.
We have begun experiments, in collaboration with Professor
Seth Love’s group in Bristol, examining the protein alphasynuclein which builds up in brain cells in MSA. In a healthy
brain specialised enzymes would usually breakdown and
clean out any alpha-synuclein that has accumulated.
However, we believe that these enzymes are probably not
working effectively in MSA, causing build-up of this sticky
protein and we are keen to find reasons for this.
By examining the levels and activity of enzymes in a large
number of MSA brains, comparing them to normal ‘control’
brains, we aim to confirm our hypothesis. We can grow cells
in a dish in the laboratory (called ‘in vitro’) and treat them
with a virus which carries DNA to code for alpha-synuclein
so that this protein can be produced. By adding different
combinations and concentrations of enyzmes we hope
to determine if we can improve the breakdown of alphasynuclein.
We are excited to find out the results of these experiments
as ultimately they could provide new ways to consider
treating MSA.”
Research Updates
Dr Helen Ling, Research Associate and Emeritus
Professor, Tamas Revesz are investigating a topical
subject, chronic traumatic encephalopathy:
“Repetitive head injury can cause long term irreversible
damage to the brain years after exposure to the injury.
The condition ‘chronic traumatic encephalopathy’ (CTE),
previously known as dementia pugilistica, was initially
recognised in retired boxers. We now know it can occur
in individuals pursuing other sports and activities which
may result in repetitive head trauma. The clinical symptoms
include progressive dementia, changes in personality and
speech, and balance and movement abnormalities. The
pathology is characterised by the accumulation of abnormal
tau protein. We all have tau protein in our brain but when it
clumps together, the protein no longer functions normally
and can lead to brain cell death.
We studied the brain tissue and clinical records of 268
donors with different pathological diagnoses including
progressive supranuclear palsy (PSP), Alzheimer’s disease,
corticobasal syndrome, frontotemporal lobar degeneration,
multiple system atrophy and healthy elderly individuals.
Our findings confirm that individuals with a history of
traumatic brain injury during life are more susceptible to
developing CTE pathology. Many had suffered concussion,
some had participated in sports prone to head injury such
as rugby, and some were military veterans.
We also found CTE pathology more commonly in PSP,
with around a quarter of the cases affected. This higher
incidence could be the consequence of these patients
experiencing sustained multiple falls, which are more
prevalent in this disease than in others. However, in our
cases the CTE changes were mild and they may not have
contributed to the clinical symptoms.
Dillwyn Smith, Artist in Residence at Queen Square Brain
Bank since 2013 is creating artwork which offers a unique
opportunity to engage the public with brain donation and
the techniques used in post mortem diagnostics and
research. The project is sponsored by The Virginia Keiley
Benefaction, and Francis and Renee Hock Foundation:
Through observational drawing at QSBB and from memory
in his studio, Dillwyn is producing a body of work entitled
‘Silvering the Cerebrum’. ‘Silvering’ refers to a particular
staining technique synonymous with neuropathology and
used when identifying various cells under a microscope.
The discovery of stains (also called aniline dyes) and their
application within the scientific and artistic worlds over a
hundred years ago led to the development of methods which
continue to be used in everyday pathological practice.
The interrelationship of science and art is not a new one.
Dillwyn is influenced by the artist William Morris who
experimented with aniline dyes when making his work and
whose workshop and home was 26 Queen Square, London
between 1865 and 1881 (now the site of The National
Hospital for Neurology and Neurosurgery).
Further research is needed in the near future to unravel
the mechanisms of CTE pathology as there are many
unanswered questions.”
Dillwyn’s aesthetic studies of neuropathology practice
provide alternative insights into the brain, and highlight the
important work and continued need for brain banks.
Image (top right) shows a microscopic view of abnormal
accumulation of tau protein (in brown) surrounding a blood
vessel in brain tissue affected by CTE
Following a successful exhibition in 2015, a symposium is
planned for April 2016 at the National Hospital for Neurology
where artists, scientists and members of the public will be
invited to attend, view the artwork and participate in
a discussion of the relationship between art and
medical science.
Some of the artworks are for sale with a proportion of all
sales going to Queen Square Brain Bank. Please visit the
project website: www.silveringthecerebrum.com
The image below shows the project motif and the cover
image shows cerebellum stained with luxol fast blue
by Dillwyn Smith, Artist in Residence 2013–15
Contributors
Contributors top row: Christina Murray, Dr Sonia Gandhi,
Professor Janice Holton, middle row: Dr Aoife Kiely,
Dr Helen Ling, Professor Tamas Revesz,
bottom row: Dillwyn Smith, Dr Sandrine Wauters
QSBB
A day in the life of QSBB senior research
technician, Dr Sandrine Wauters:
“My scientific career started at Warwick University
where I completed a BSc in Biological Sciences.
I took an opportunity during my degree to work at
Novartis Pharmaceuticals in Basel, Switzerland where
I used human muscle cells as part of my project.
This sparked my passion for scientific research and
I went on to do a PhD in Learning and Memory.
I knew my ultimate goal was to study the mechanisms
involved in neurodegenerative diseases and in
September 2014 I began working at QSBB as a
senior research technician.
I feel privileged to have this unique position where
I can contribute to research as well as to the day to
day running of the brain bank. Last year we had a
Human Tissue Authority (HTA) inspection lasting two
days (brain banks are required by law to be licensed
with the HTA) and I helped to log all frozen tissue
from over two thousand brains which are stored here
in freezer rooms. I also recently trained as a medical
photographer and during the weekly brain dissection
I can now take high quality images which are often
used in medical education and displayed at
scientific meetings worldwide.
My own experiments involve utilising brain tissue
from donors who had multiple system atrophy (MSA)
in life, as part of a project funded by the Multiple
System Atrophy Trust. The brain bank provides a
valuable resource of tissue matched with donors’
medical records. One of my first tasks was to create
a database detailing all 232 MSA cases, the largest
collection in the UK, with the pathological and
clinical information. This now serves as a resource
for researchers studying this poorly understood
degenerative condition.
It is a real pleasure and honour to work at QSBB,
every day is interesting, and I hope to continue to
participate in new projects for the foreseeable future.”
Donations
The importance of controls
We would like to encourage people without a neurological
condition, ‘controls’ to register with our donor scheme.
Controls are vital in providing researchers with an
understanding of the normal appearance and function of
the brain, and for comparison with the diseased brain.
Brain donation coordinators
Lynn Haddon, who recently joined QSBB as
administrator, is the first point of contact for potential
donors. She is responsible for coordinating the
brain donor scheme and along with Linda Parsons,
laboratory manager and Robert Courtney, senior
technician, organise the safe receipt of donated brains.
Lynn, Robert and Linda provide an on-call service
during evenings and weekends, and liaise with
relatives, hospital staff, funeral directors and couriers,
to ensure the careful donation of the brain with the
minimum of distress to the relatives of the deceased.
Coordinators from left to right: Lynn Haddon,
Linda Parsons and Robert Courtney
If you would like further information you can log on to the
website: www.ucl.ac.uk/qsbb. Or contact Lynn Haddon
on 020 7837 8370 or l.haddon@ucl.ac.uk
Brain banking
Brain banking is expensive and we continue to depend
entirely on charitable benefactions for our survival.
The QSBB is primarily funded by donations from the
Reta Lila Weston Institute of Neurological Studies.
The Amanda Fund has been set up to raise money for
QSBB in memory of Mrs Amanda Jane Hill, whose family
are generously supporting our research. We are grateful to
several other benefactors, in particular The PSP Association
and The Virginia Keiley Benefaction, and would also like to
extend our appreciation to Mr Roy Anderson who ran the
Milton Keynes Marathon to raise funds for the QSBB.
If you would like to offer a charitable donation to support
our work, please contact Lynn Haddon.
Please let us know if you change your address or any of
your details.
Thank you again for your support.
Sponsors
Supranuc
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r Palsy
lea
Progress
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Reta Lila Weston Institute
of Neurological Studies