Alzheimer’s Disease – eUpdate

Studies Find Possible New Genetic Risk Factors for Alzheimer’s Disease

NIH-funded genome-wide association study is largest ever conducted in Alzheimer’s research

from the Alzheimer’s Disease Education and Referral Center:

Studies find possible new genetic risk factors for Alzheimer's Disease

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Scientists have confirmed one gene variant and have identified several others that may be risk factors for late-onset Alzheimer’s disease, the most common form of the disorder. In the largest genome-wide association study, or GWAS, ever conducted in Alzheimer’s research, investigators studied DNA samples from more than 56,000 study participants and analyzed shared data sets to detect gene variations that may have subtle effects on the risk for developing Alzheimer’s. The National Institutes of Health funded the study appearing April 3, 2011, in the online issue of Nature Genetics.

“New technologies are allowing us to look at subtle genetic differences among large groups of study participants. By comparing people diagnosed with Alzheimer’s with people free of disease symptoms, researchers are now able to discern elusive genetic factors that may contribute to risk of developing this very devastating disease,” said Richard J. Hodes, M.D., director of the National Institute on Aging (NIA). “We are entering an exciting period of discoveries in genetics that may provide new insights about novel disease pathways that can be explored for development of therapies.”

The Alzheimer’s Disease Genetics Consortium (ADGC), a collaborative body established and funded by the NIA, part of the NIH, coordinated the study. The research reported today involved investigators at universities and research centers across the country. Datasets were funded in part by the NIA, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the National Center for Research Resources, all part of the NIH. The Alzheimer’s Association, U.S. Department of Veterans Affairs, Wellcome Trust, Howard Hughes Medical Institute, and the Canadian Institute of Health Research also lent support. Gerard Schellenberg, Ph.D., University of Pennsylvania School of Medicine, Philadelphia, directs the ADGC, which also received Recovery Act funds in 2009.

Until recently, only one gene variant, Apolipoprotein E-e4 (APOE-e4), had been confirmed as a significant risk factor gene for the common form of late-onset Alzheimer’s disease, which typically occurs after age 60. In 2009 and 2010, however, researchers confirmed additional gene variants of CR1, CLU and PICALM as possible risk factors for late-onset Alzheimer’s. This newest GWAS confirms that a fifth gene variant, BIN 1, affects development of late-onset Alzheimer’s. It also identified genetic variants significant for Alzheimer’s at EPHA 1, MS4A, CD2AP, and CD33. The genes identified by this study may implicate pathways involved in inflammation, movement of proteins within cells, and lipid transport as being important in the disease process.

In addition, a second paper appearing online in the journal presented GWAS findings for Alzheimer’s by another scientific team. The United Kingdom-based group, led by Julie Williams, Ph.D., Cardiff University School of Medicine, Wales, found the same genes as risk factors and identified a gene variant ABCA7 as an additional gene of interest. Components of the NIH involved in or supporting the study included the NIA, the National Heart, Lung and Blood Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases. Some private support came through the independent Foundation for the National Institutes of Health.

“Researchers conducting GWAS are looking for genetic variations that may have a smaller effect but still play a role in the disease,” said Schellenberg. “Our findings bring us one step closer to a fuller understanding of the genetic basis of this complex disease, although more study is needed to determine the role these genetic factors may play in the onset and progression of Alzheimer’s.”

Schellenberg said the study was made possible by the research infrastructures established and funded by the NIA, including 29 Alzheimer’s Disease Centers, the National Alzheimer’s Coordinating Center, the Genetics of Alzheimer’s Disease Data Storage Site, the Late-onset Alzheimer’s Disease Family Study, and the National Cell Repository for Alzheimer’s Disease. They collect, store and make available to qualified researchers DNA samples, datasets containing biomedical and demographic information about participants, and genetic analysis data.


Naj, A.C., et al. Common variants of MS4A4/MS4A6E, CD2AP, CD33 and EPHA 1 are associated with late-onset Alzheimer’s Disease. Nature Genetics. Epub April 3, 2011.

Hollingworth, P., et al. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA 1, CD33 and CD2AP are associated with Alzheimer’s disease. Nature Genetics. Epub April 3, 2011.

The NIA leads the federal government effort conducting and supporting research on aging and the health and well being of older people. For more on health and on aging generally, go to The NIA provides information on age-related cognitive change and neurodegenerative disease specifically at its Alzheimer’s Disease Education and Referral (ADEAR) Center at To sign up for e-mail alerts about new findings or publications, please visit either website.

The 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

The activities described in this release are being funded through the American Recovery and Reinvestment Act (ARRA). To track the progress of HHS activities funded through the ARRA, visit To track all federal funds provided through the ARRA, visit