U.S. NATIONAL INSTITUTES OF HEALTH
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LEADING THE FEDERAL EFFORT ON AGING RESEARCH

Major AD Research Initiatives


The NIA continues to support several major initiatives in which the clinical, genetic, imaging, and biological data and samples that are collected are being made widely available to qualified investigators through secure web-based systems. As a result, these initiatives have become a critical national and international resource for scientists who are interested in AD, other neurodegenerative diseases, healthy aging, and related topics.

Alzheimer’s Disease Genetics Initiative

two older women smilingGenetic studies of complex neurodegenerative diseases such as AD have focused on two key issues—whether a gene might influence a person’s overall risk of developing a disease and whether a gene might influence some particular aspect of a person’s risk, such as the age at which the disease begins. So far, scientists have discovered three mutations that cause the rare early-onset form of familial AD and one mutation that affects the risk of developing late-onset AD (see "Beta-amyloid and Its Damaging Effects on Neurons" for more on these genes). Scientists estimate that an additional four to seven risk factor genes exist for late-onset AD. Evidence uncovered by NIA investigators also suggests that variability in the genes that cause early-onset AD may increase the risk of developing late-onset AD (Myers et al., 2005; Singleton et al., 2004).

As AD genetics research has intensified, it has become increasingly clear that scientists need many samples of genetic material if they are to continue making progress in identifying new risk factor genes, as well as identifying associated environmental factors and understanding the interactions of genes and the environment. These advances will ultimately allow investigators to identify people at high risk of developing AD and help them focus on new pathways that may be amenable to prevention or treatment.

The goal of the NIA Genetics Initiative is to identify at least 1,000 families with members who have late-onset AD as well as unaffected family members, and encourage these individuals to provide blood samples and other clinical data for the initiative. More than 900 families already have been recruited but more are needed, so NIA is providing funding to the ADCs to help recruit the remaining participants. The NIA ADEAR Center is collaborating with the Alzheimer’s Association to develop media and community outreach programs to foster participation in the initiative among families who have two or more living members with late-onset AD.

The Genetics Initiative collects blood samples and other clinical data from people with AD and their unaffected familiy members. This allows investigators to create and maintain “immortalized” cell lines—cells that are continuously regenerated in the laboratory. These cell lines are crucial for the exhaustive DNA analysis studies needed to identify risk factor genes, each of which may have relatively small effects on AD development. The National Cell Repository for AD (NCRAD), located at Indiana University, serves as the centralized repository for the initiative (http://ncrad.iu.edu), providing DNA and cell lines to qualified investigators for genetics studies. In 2006, NIA opened the Genetics of Alzheimer’s Disease Data Storage Site at Washington University. Scientists who use NCRAD samples and data and AD geneticists funded by NIA are asked to submit published genetics data to the Storage Site for additional analysis by qualified investigators. An initial subset of cases has recently undergone a whole genome scan, and results are now available on the website. Many AD researchers also are taking advantage of a large sample repository and genetics database already developed by NIMH. Beginning in 2006, data from combined NIMH and NIA sample sets will be available through a unique data repository shared by the two Institutes.

Alzheimer’s Disease Neuroimaging Initiative

NIA has launched the multi-year AD Neuroimaging Initiative, which will use serial MRI and PET scans to examine how brains change as MCI and AD progress. The project will follow approximately 200 cognitively healthy individuals for 3 years, 400 people with MCI for 3 years, and 200 people with early AD for 2 years. Funding for the initiative began in 2004 and enrollment of participants is nearly complete. By using MRI and PET scans at regularly scheduled intervals, investigators hope to learn when and where in the brain degeneration occurs as memory problems develop.

Scientists will correlate this imaging information with clinical, neuropsychological, and biological markers from blood, cerebrospinal fluid, and urine samples collected at intervals from individuals in the study. Potential markers include levels of beta-amyloid and tau, indicators of inflammation, and measures of oxidative stress. Rigorous imaging and biomarker standards developed as a result of this initiative will help in early diagnosis and provide measures for the success of potential treatments. This would substantially increase the pace and decrease the cost of developing new treatments.

This initiative is a partnership among the NIA, university investigators, the pharmaceutical and imaging equipment industries, the FDA, and the NIH Foundation, with participation from the Alzheimer’s Association and the Institute for the Study of Aging. An important aspect of this initiative is that the clinical, imaging, and biological data collected will be shared and made available to all qualified scientific investigators for further analyses. For more information about the Neuroimaging Initiative, visit www.nia.nih.gov/Alzheimers.

The Cognitive and Emotional Health Project

older manA large number of people are at substantial risk for cognitive impairment from many causes as they age. The same is true for emotional disorders. Although research into biological mechanisms and environmental and social effects is yielding promising results in both animal and human studies, much remains to be discovered. These gaps in current knowledge spurred NIA, NINDS, and NIMH to jointly create the trans-NIH Cognitive and Emotional Health Project: The Healthy Brain. This initiative will spur advances in understanding changes in cognition and emotion in adulthood and what can be done to preserve and enhance positive outcomes—advances that are central to the missions of the participating Institutes. The overall goal of the Cognitive and Emotional Health Project is to assess the state of longitudinal and epidemiologic research on demographic, social, and biologic determinants of cognitive and emotional health in aging adults, and to accelerate identification of ways to maintain cognitive and emotional health. The Project also is examining the pathways by which cognitive and emotional health may influence each other. Project staff have completed a detailed evaluation of the scientific literature on factors involved in maintaining cognitive and emotional health in adults (Hendrie et al., 2006). The NIH Blueprint for Neuroscience Research has funded a 5-year effort to create the NIH Toolbox for Assessment of Neurological and Behavioral Function (www.neuroscienceblueprint.nih.gov). This effort will use state-of-the-art research and novel testing methods to develop an integrated set of measures of cognitive, emotional, and sensory health. These measures will be appropriate for use in large-scale studies and clinical trials. For more information on project activities currently underway to accomplish these goals, visit http://trans.nih.gov/CEHP.

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Page last updated Jul 28, 2007

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