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Genes involved in age-related declines in brain volume may play role in Alzheimer's disease

The hippocampus, a brain region important to learning and memory, gradually loses volume as part of the normal aging process. This loss is significantly accelerated in older people with Alzheimer’s disease, especially if they have vascular problems or diabetes.   Now, an international team of researchers has identified four genes that may play a role in the age-related decline of hippocampal volume, a finding that may provide insight to risk for cognitive decline and Alzheimer’s disease. Conducted in part by NIA-funded investigators, the study appeared online April 15, 2012, in Nature Genetics.

The findings result from the combined analyses of several genome-wide association studies (GWAS) conducted in the U.S., Canada, Europe and Australia involving thousands of participants with and without Alzheimer’s disease. GWAS analyze DNA to identify specific genetic variations associated with particular diseases. The researchers located four gene risk factors on chromosome 12 that may play a role in age-related hippocampal decline.  

The genes implicated in the findings are involved in cell death, brain development and plasticity, oxidative stress and enzymes targeted by diabetes medications—all of which may contribute to the brain’s vulnerability to Alzheimer’s. While we need to learn more about the complex interplay between genetic risk for Alzheimer’s disease and other factors that influence its onset and progression, these genes findings on age-related declines in brain volume could lead to new approaches for the devastating hippocampal declines wrought by the disorder.

Reference: Bis JC, et al. Common variants at 12q14 and12q24 are associated with hippocampal volume. Nature Genetics. doi:10.1038/ng.2237