2013 Zenith Fellows
It is my pleasure to share with you the 2013 Zenith Fellows chosen this past week at the annual
meeting in New York. Due to the continued support and passion of the Zenith Society, I am
pleased to announce that a total of four researchers will receive a Zenith fellowship. Since its
inception in 1991 the Alzheimer’s Association’s Zenith Society has provided more than $30
million in Zenith Fellows Awards to more than 100 leading Alzheimer’s disease researchers
worldwide.
These grants support senior scientists who have contributed significantly to the field of
Alzheimer's disease research and whose proposed project is highly likely to make new
contributions to the Alzheimer's field. Through your generosity, you have helped to advance
scientific knowledge of the causes of Alzheimer’s disease that can lead to effective treatments,
as well as supporting the needed care of affected individuals.
Now in its 23rd year, the Alzheimer’s Association Zenith Society has a heritage of fostering
cutting-edge research in Alzheimer’s disease and related dementia. The 2013 Zenith Fellows
promise to continue this tradition of progress and innovation. In the summaries below, they
address fundamental questions about the biology of Alzheimer’s disease, and ways to prevent,
diagnose or treat the disease.
The first Zenith recipient, Scott Brady, Ph.D., and colleagues from University of Illinois Chicago, propose to study why branchlike structures of certain neurons—extensions used to
transmit and receive chemical signals—begin to shrink and become less active in Alzheimer’s
disease. Earlier research has found that cellular proteins called molecular motors may lose their
ability to transport nutrients to these branchlike structures, possibly hindering the structures’
function. Dr. Brady and colleagues hope to identify how such nutrient transport is affected
by Alzheimer's-related brain changes, especially those linked to abnormal beta-amyloid and tau
activity. The study’s results could shed new light on why people with Alzheimer's disease and
related dementia tend to lose certain kinds of neurons.
Our second awardee, Benjamin Wolozin, Ph.D., and colleagues from Boston University
Medical Campus, propose to study how genetic changes may promote the clumping of harmful
tau into the “tangles” observed in Alzheimer’s and related dementia. Specifically they are
examining the role of molecules that bind to RNA (ribonucleic acid), the long-stranded
compound that translates the genetic code from genes into proteins. Previous studies have
shown that when cells are under stress, RNA-binding proteins may form clumps called “stress
granules,” which store RNA for later use. Dr. Wolozin and his team have observed that tau
tends to interact with RNA-binding proteins located in stress granules. Such interactions, they
hypothesize, may make tau more likely to accumulate abnormally under stressful conditions—
including early Alzheimer’s disease. The researchers seek to test this novel hypothesis.
Our third awardee, Stephen Strittmatter, M.D., Ph.D., and colleagues from Yale University,
propose to assess a mechanism that may harm synapses in the brain. Synapses are
specialized gaps between nerve cells through which cells communicate by sending and
receiving chemical signals. As such, they are vital for maintaining cellular communication. Dr.
Strittmatter’s team has found that a protein called mGluR5 (metabotropic glutamate receptor 5),
which exists in a specific area of the synapse, may become abnormally active in Alzheimer’s
disease. This activity may lead to synaptic damage, possibly by enhancing the toxic functions of
beta-amyloid and tau—two proteins implicated in dementia-related brain changes. The
researchers hope to learn more about how mGluR5 may harm brain cell health and to test
whether blocking mGluR5 activity in Alzheimer’s-like mice may prevent synaptic loss in these
animals. The results of Dr. Strittmatter’s work could lead to novel therapies for slowing the
progression of Alzheimer’s in people.
Our fourth and final awardee, Agueda Rostagno, Ph.D., and colleagues from New York
University School of Medicine, propose to study how “oligomers” may damage endothelial cells
that line the inside surface of blood vessels. Oligomers are intermediate clumps of beta-amyloid
that occur before they development into plaques, a hallmark of Alzheimer's disease, and may
be responsible for causing early brain cell dysfunction. In another disease, cerebral amyloid
angiopathy (CAA), amyloid plaques clog blood vessels that supply blood to the brain. Yet in
both Alzheimer’s and CAA, beta-amyloid may become most toxic when it forms smaller
oligomer clumps. According to the team’s hypothesis, oligomers damage the energysupplying structures called "mitochondria" inside the endothelial cells. The researchers will test
their hypothesis by examining whether a drug called methazolamide, which protects
mitochondrial function, can prevent oligomer-related damage to blood vessels in the brain when
blood flow is reduced. This effort will involve studies with cells grown in a dish and with mice
engineered to develop Alzheimer’s-like brain changes and CAA. Results of Dr. Rostagno’s work
could improve our understanding of how CAA and Alzheimer’s are related.
The Alzheimer's Association is ever grateful for your steadfast support. It is because of your
leadership that we are able to continue to push the field forward by investing in new and
innovative ways through the Zenith Fellows Awards of the International Research Grant
Program. We thank you for joining us in our vision of a world without Alzheimer's disease and
hope to thank you in person at upcoming Zenith Society experiences, including the summer's
Alzheimer's Association International Conference in Copenhagen.
Sincerely,
Maria C. Carrillo, PhD, Vice President
Medical & Scientific Relations, Alzheimer's Association