Alzheimer's Risk Genes Linked to Brain Atrophy

A direct link has been found of common variants of two genes to atrophy in cortical and hippocampal regions of the brain, which are associated with memory and other key functions. It is also believed to be the first to link the atrophy to protein levels in the blood produced by the genes.

Neurobiologists at the Indiana University School of Medicine (Indianopolis, IN, USA) and their colleagues conducted a study in 50 participants with no cognitive difficulties and 90 who had been diagnosed with mild cognitive impairment, a condition that is associated with increased risk of developing Alzheimer's disease. All of the participants were 50 years or older. The team investigated the top nine genetic variants that have been associated with Alzheimer's disease risk, not including the apolipoprotein E (APOe4) gene that has long been linked to increased risk for several characteristics of Alzheimer's disease.

The team used magnetic resonance imaging tools to measure brain size and genetic analysis, the scientists looked for associations between the genetic variants and atrophy in the cortical and hippocampal regions of the brain, which are established physical biomarkers of Alzheimer's disease. Peripheral blood expression array data was obtained using the 1-million SNP Illumina Human Omni-Quad array and Illumina Human BeadChips (Illumina; San Diego, CA, USA). After explicit matching of cortical and hippocampal morphology they computed in 3D the cortical thickness and hippocampal radial distance measures for each participant.

The scientists found that just two genetic variants of the Membrane-Spanning 4-Domains, Subfamily A, Member 6A (MS4A6A rs610932) and the ATP-Binding Cassette, Sub-Family A (ABC1), Member 7 (ABCA7 rs3764650) were significantly associated with cortical and hippocampal atrophy. Exploratory MS4A6A and ABCA7 peripheral blood expression analyses revealed a similar pattern of associations with cortical neurodegeneration.

Liana G. Apostolova, MD, the Barbara and Peer Baekgaard, professor of Alzheimer's Disease Research and senior author of the study said, “We also found that the levels of the protein products of these genes, circulating in the peripheral blood, were associated with the cortical and hippocampal atrophy. This finding suggests that those results of gene expression could become useful biomarker blood tests for Alzheimer's disease.” The study was published online on November 05, 2015, in the journal Neurobiology of Aging.

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