Date Published: 4 April 2011

Recent research suggests possible genetic risk factors for Alzheimers Disease

Identification of possible genetic risk factors for Alzheimer's Disease has resulted from recent research conducted in the United States.

Scientists have confirmed one gene variant and have identified several others that may be risk factors for Alzheimer's disease (specifically late-onset Alzheimer's disease), the most common form of Alzheimer's Disease. In the largest genome-wide association study (sometimes referred to as GWAS), ever conducted in Alzheimer's research, investigators studied DNA samples from more than 56,000 study participants and analysed shared data sets to detect gene variations that may have subtle effects on the risk for developing Alzheimer's Disease.

" 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) is a collaborative body established and funded by the National Institute on Aging (NIA) and coordinated this study. The research involved scientists working at many universities and research centers across the United States. Datasets were funded in part by the NIA and many other organisations.

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. Then in 2009 and 2010, scientific researchers confirmed additional gene variants of CR1, CLU and PICALM as possible risk factors for Alzheimer's Disease (specifically late-onset Alzheimer's). This recent research 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.

Another paper also appearing online in the journal "Nature Genetics" 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 for Alzheimer's Disease and identified a gene variant ABCA7 as an additional gene of interest. See 2nd paper listed below.

" 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.

References to Papers
* 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.S

About NIH:
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 - statement understood to be correct as of publication date.

Source: National Institutes of Health (NIH), USA.

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