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Study Identifies Two Gene Variants Associated With Late-Onset Alzheimer's Risk BETHESDA, Md -- September 7, 2009 -- Researchers have identified 2 new possible genetic risk factors for late-onset Alzheimer’s. The study, which pooled DNA samples from a number of European and U.S. groups, not only associated variations in the sequence of the CLU and PICALM genes with increased risk, but also found another 13 gene variants that merit further investigation. The findings are published in the September 6 online issue of the journal Nature Genetics. To date, only 4 genes have been definitively associated with Alzheimer’s disease. Three mutated genes-amyloid precursor protein (APP) and the presenilins (PS1 and PS2)-have been shown to cause the rare, early-onset familial form of the disease, which mostly occurs in middle age. Only 1 gene variant, apolipoprotein e4 or APO-e4, has been confirmed as a significant risk factor gene for the common form of late-onset Alzheimer’s. The study, led by Julie Williams, PhD, School of Medicine at Cardiff University, Wales, United Kingdom, used brain and blood tissues made available and analysed by dozens of laboratories in the United Kingdom, Ireland, Germany, Belgium, Greece, and the United States. The 2-stage study first used samples from people with Alzheimer’s and a control group free of the disease to locate CLU on chromosome 8 and PICALM on chromosome 11, and then replicated the findings in a second stage of testing. CLU (ApoJ/clusterin located on chromosome 8) and PICALM (phosphatidylinositol-binding clathrin assembly protein located on chromosome 11) are both potentially involved in important pathways involved in Alzheimer’s disease. While more study is needed to determine the roles of the CLU and PICALM variants in Alzheimer’s pathology, the researchers noted that CLU levels are often elevated when brain tissue is injured or inflamed. Increased levels of CLU are found in the brains and cerebrospinal fluids of Alzheimer’s patients. SOURCE: National Institutes of Health E-mail this page to a friend or colleague! To print, use this version