Recovery Funds Advance Alzheimer's Disease Research
American Recovery and Reinvestment Funds are being used to promote the national
research efforts to better understand, diagnose and treat Alzheimer's disease.
The National Institute on Aging (NIA), part of the National Institutes of Health,
has targeted promising areas of research in granting the awards, such as new
and ongoing studies to identify additional risk factor genes associated with
Alzheimer's, improve diagnostic tools, find biomarkers, develop therapies, conduct
clinical trials and explore preventive measures.
"We are delighted to announce the award of Recovery Act funds to many dedicated,
hardworking scientists committed to advancing scientific discovery into Alzheimer's
disease and cognitive impairment," said NIA Director Richard J. Hodes, M.D. "Over
the next two years, the recipients will use this unprecedented boost in research
funds to help reach our ultimate goal of understanding age-related cognitive
decline and reducing the individual and societal burden of this devastating disease."
More than 100 Alzheimer’s or Alzheimer's-related research grants were awarded
under the Recovery Act. The full list of NIH grants can be found at http://grants.nih.gov/recovery/.
The grants featured here highlight how these funds will expand research. Some
of the funding will advance the work of existing NIA initiatives that benefit
from large-scale collaborative, interdisciplinary research:
The Neuroimaging Initiative — Identifying brain changes before symptoms appear
The Alzheimer's Disease Neuroimaging Initiative (ADNI) will receive $24 million
in stimulus funds — half from the NIA and half contributed by the NIH Office
of the Director — to further groundbreaking research to establish neuroimaging
and biomarker measures. These funds will enable researchers — and ultimately
practicing physicians — to track changes in the living brain as older people
transition from normal cognitive aging to amnestic mild cognitive impairment
(MCI), in which individuals have a memory deficit but generally retain other
cognitive abilities, and from MCI to Alzheimer’s disease. ADNI, a research partnership
supported primarily by the NIA with private sector support through the Foundation
for NIH, seeks to find neuroimaging and other biological markers that can be
used to detect Alzheimer's disease progression and measure the effectiveness
of potential therapies.
The original ADNI involved the study of 800 people who ranged from normal to
those with late-stage MCI or overt Alzheimer’s disease. This new grant expands
the scope of ongoing research under ADNI by allowing for the enrollment of participants
at an earlier stage of MCI, when symptoms are milder. Furthermore, the funding
for this new grant will allow ADNI investigators to extend the length of the
original study to better assess changes in individuals over time. All of the
participants will have neuroimaging scans and blood and cerebrospinal fluid analyses
to look for changes in the brain.
The overall impact of the added funding will be increased knowledge of the sequence
and timing of events leading to MCI and Alzheimer’s disease and development of
better clinical and imaging/fluid biomarker methods for early detection and for
monitoring the progression of these conditions. This will facilitate clinical
trials of treatments to slow disease progression and will ultimately contribute
to the prevention of Alzheimer’s disease. Just this year, ADNI made a significant
step forward in developing a test to help diagnose the beginning stages of Alzheimer’s
disease sooner and more accurately by measuring levels of two biomarkers — tau
and beta-amyloid proteins — in cerebrospinal fluid.
"Researchers and clinicians need imaging and biomarker tools to detect
and understand the very earliest signs of pathology that cause changes in the
brain some 10 to 20 years before any clinical symptoms of cognitive impairment
or Alzheimer's may appear,"said ADNI Principal Investigator Michael Weiner, M.D., of the San
Francisco Department of Veterans Affairs Medical Center and the University of
California, San Francisco. "This grant will help us in our goal of establishing
a panel of biomarkers that predict those at risk of developing the disease and
also reveal which therapies may be effective in treating the disease or preventing
its progression."
The grant was awarded to the Northern California Institute for Research and Education,
a nonprofit research foundation affiliated with the San Francisco VA Medical
Center. ADNI is the largest public-private partnership on brain research under
way at the NIH. In addition to the NIA, the federal ADNI partners are the National
Institute of Biomedical Imaging and Bioengineering, also part of NIH, and the
U.S. Food and Drug Administration, another agency of the U.S. Department of Health
and Human Services.
The AD Genetics Consortium and more " Identifying genes affecting risk for late-onset
Alzheimer’s
A grant of more than $5.4 million will add 3,800 Alzheimer's patients and an
equal number of people free of the disease to a previously funded study by the
Alzheimer’ Disease Genetics Consortium (ADGC). Gerard Schellenberg, Ph.D., University
of Pennsylvania School of Medicine, Philadelphia, leads the consortium, which
aims to identify the additional risk factor genes for late-onset Alzheimer's
disease. All of these study participants are currently enrolled in the NIA-funded
national network of 29 Alzheimer's Disease Centers. When added to the samples
from other sources, this will make available one of the largest collections of
samples to perform genome-wide association studies (GWAS) in an effort to identify
the susceptibility and protective genes influencing the onset and progression
of late-onset disease. The large number of DNA samples brought together in this
study may enable the researchers to detect genes whose individual effects in
the disorder may be small but may still play a role.
The ADGC will use research infrastructures previously established by NIA to store
and make available to qualified researchers DNA samples, datasets containing
a wealth of information about participants, and genetic analysis data. The combined
resources will allow scientists also to search for genes associated with a number
of traits associated with Alzheimer's, as well as for genes related to cognitive
decline.
"This funding will bring us closer to identifying the elusive genetic variations
that contribute to overall risk and development of late-onset Alzheimer's disease," said
Marcelle Morrison-Bogorad, Ph.D., director of the NIA Division of Neuroscience. "With
this large sample size and the rapid DNA sample and data sharing, there are tremendous
opportunities for defining new disease pathways that could lead to the development
of new therapies."
Additionally, $4.7 million in Recovery Act funds will be used for another important
study — a GWAS project examining cognitive decline in older African-Americans.
Denis Evans, M.D., of Rush University Medical Center in Chicago, will collect
and analyze the DNA of 4,140 elderly African-Americans enrolled in NIA-funded
aging studies already taking place in Chicago and Indianapolis. Data from this
analysis will also be shared with the ADGC to help identify risk factor genes
for cognitive decline and late-onset Alzheimer's. The study will assess the associations
of over 900,000 genetic markers with other co-morbidities, including stroke and
high blood pressure.
Another $820,000 in Recovery Act funds will advance Alzheimer's genetics research
by developing methods for identifying combinations of genes that might influence
age-related risk of AD. The role of different forms of translocase of outer mitochondrial
membrane (TOMM40), a gene that makes a protein thought to play a role in disease
onset, will be studied by Allen Roses, M.D., of the Duke University School of
Medicine in Durham, N.C.; Roses discovered the link between the apolipoprotein
E (APOE)-epsilon 4 gene and increased risk for late-onset Alzheimer's disease.
This new study will investigate whether particular variants of TOMM40 that tend
to co-occur with the APOE3 gene also interact with that gene, and if this interaction
plays a role in the age of disease onset.
Additional Recovery Act research opportunities
Other studies made possible by the Recovery Act range from clinical trials to
epigenomic studies to translational research:
Drug, exercise clinical trials — A clinical trial exploring whether
low doses of an anti-epileptic seizure drug, levetiracetam, can improve memory
and affect brain function in people with MCI will be conducted with $1.2 million
in support. Michela Gallagher, Ph.D., of Johns Hopkins University, Baltimore,
will use functional MRI to visualize activity in the hippocampus — a brain area
that becomes overactive in MCI patients — while the clinical trial participants
receiving either the drug or a placebo engage in memory tasks. In another trial,
researchers will examine how exercise training, cognitive training, or a combination
of both, might impact immune and inflammatory biomarkers and cognitive health
in older adults with MCI. The randomized trial, under a $1 million grant to David
Lowenstein, Ph.D., of the University of Miami, will examine a broad array of
outcomes and will include Hispanic and non-Hispanic volunteers.
Epigenetics/translational research — A $1 million grant will support
a study exploring whether changes in histone acetylation (an epigenetic, or non-genetic
factor that causes genes to behave differently) are one way in which a variety
of life experiences may influence the risk of developing age-related cognitive
decline and dementia. David Bennett, M.D., of Rush University Medical Center,
Chicago, will use brain tissues from the NIA-funded Memory and Aging Project
and the Religious Orders Study to examine this question. Another epigenomics
grant of $819,000 will be used in translational research to test whether overexpressing
histone deacetylase (HDAC1) with small molecule probes in the brain may demonstrate
therapeutic potential for Alzheimer’s and stroke patients. Li-Huei Tsai, Ph.D.,
of Massachusetts Institute of Technology, Boston, will lead the study, which
seeks to find out whether abnormal regulation of the protein may play a role
in neurological disorders.
The NIA leads the federal effort supporting and conducting research on aging and the medical, social and behavioral issues of older people. For more information on research and aging, go to www.nia.nih.gov.The NIA provides information on age-related cognitive change and neurodegenerative disease specifically at its Alzheimer’s Disease Education and Referral (ADEAR) Center site at www.nia.nih.gov/Alzheimers. To sign up for e-mail alerts about new findings or publications, please visit either website.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
The activities described in this release are being funded through the American Recovery and Reinvestment Act. More information about NIH’s Recovery Act grant funding opportunities can be found at http://grants.nih.gov/recovery/. To track the progress of HHS activities funded through the Recovery Act, visit www.hhs.gov/recovery. To track all federal funds provided through the Recovery Act, visit www.recovery.gov
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