Alzheimer’s disease is a progressive illness that is the leading cause of dementia and the sixth leading cause of death in the United States. There is no cure for the disease, with current available treatments only slowing and not stopping, the deterioration. Although scientists have been linking a growing number of gene variants to the risk of developing Alzheimer’s disease, most of the associations have not yet identified the specific mechanisms that would increase the risk of developing the disease. Now, a study from researchers at Indiana University shows that two genetic variants previously linked to Alzheimer’s disease cause the brain atrophy that is characteristic of the disease. The team state that the brain atrophy-linked proteins produced by the ‘risk’ genes, circulate in the blood and could be used in Alzheimer’s-related tests in the future.
Previous studies show that Alzheimer’s disease is triggered by interactions of multiple genetic and epigenetically-based environmental factors. The APOE gene E4 allele is the best-known risk factor for Alzheimer’s disease, yet it represents a small ratio of genetic factors. Numerous genome-wide association studies have identified several novel genes associated with the risk of Alzheimer’s disease. However, most of these novel genes haven’t been validated through replication in separated populations. To add to this, the precise physiologic function of many of the recently discovered Alzheimer’s disease risk variants remains unknown, with the downstream effects of genetic variants largely unexplored. The current study identifies the top nine genetic variants that have been associated with Alzheimer’s disease risk, not including the APOe4 gene which has long been linked to increased risk for several characteristics of Alzheimer’s disease.
The current study uses magnetic resonance imaging to look 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. The studies were conducted 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. Results show that after explicit matching of cortical and hippocampal morphology computed in 3D, just two of the genetic variants, known as ABCA7 and MA4A6A, appeared to be associated with the changes in brain structure.
Data findings show that exploratory MS4A6A and ABCA7 peripheral blood expression analyses revealed a similar pattern of associations with cortical neurodegeneration. The lab state that, to their knowledge, their study is the first to directly link common variants of the genes, ABCA7 and MA4A6A, to atrophy in cortical and hippocampal regions of the brain, which are associated with memory and other key functions.
The team surmise that their findings are the first to link the atrophy to protein levels in the blood produced by the genes. For the future, the researchers state that the levels of the protein products of these genes circulating in the peripheral blood, associated with the cortical and hippocampal atrophy, could become biomarker blood tests for Alzheimer’s disease.