Large Study Reveals New Risk Genes for Alzheimer’s Disease

 

Analysis of genetic data from more than 94,000 people has revealed new risk genes for Alzheimer’s disease (AD) and confirmed 20 known others. Researchers also reported that mutations in genes specific to tau protein might play an earlier role in the disease than previously thought. 

These new findings, published online in Nature Genetics, support evidence that genes in biologic processes such as cell trafficking, lipid transport, inflammation, and the immune response are “genetic hubs” important to the disease process. The researchers analyzed common and rare gene variants in people with late-onset AD. In addition to confirming 20 known genes for risk of the disease and identifying 5 additional AD-related genes, cellular pathway analysis implicated the immune system, lipid metabolism, and amyloid precursor protein (APP) metabolism in the disease process. 

The study suggests that variants affecting APP and amyloid-ß processing are associated with early-onset autosomal dominant AD and late-onset AD. For the first time, the study implicated a genetic link to tau-binding proteins. The data suggest that therapies for patients with early-onset AD could also be applied to those with late-onset disease as well. 

A key to these discoveries was the sample size for the research, the largest ever for this type of study. “Having more and more samples in genome-wide association studies (GWAS) data sets is like adding more and more pixels to a photograph—it helps researchers see details that they otherwise wouldn’t and helps them decide where to focus further study,” said Marilyn Miller, PhD, director of the Genetics of Alzheimer’s Disease program at the National Institute on Aging.  

 

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