Recovery Funds Advance Alzheimer's Disease Research
News Nov 30, 2009
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 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.