Genes Linked to Why Women Are More Prone to Alzheimer’s

by Mark Terry for Biospace:It is well-known that women are more likely to get Alzheimer’s disease than men, but exactly why hasn’t been clearly understood. Research presented at the Alzheimer’s Association International Conference (AAIC) in Los Angeles today describes several genes linked to the disease only in men and others related to risk only in women.Brian Kunkle, a genetic epidemiologist and associate scientist at the University of Miami, along with genomics teams at several institutions, analyzed two large datasets from the Alzheimer’s Disease Sequencing project whole-exome sequencing study. The goal was to identify possible additional sex-specific genetic associations with Alzheimer’s.Replication analysis was conducted using the Alzheimer’s Disease Genetics Consortium (ADGC) Haplotype Reference Consortium.According to Kunkle, “Women comprise nearly two-thirds of all Alzheimer’s disease (AD) cases, suggesting sex-specific risk and protective factors. For example, a number of studies have established that apolipoprotein E (APOE) genotype contributes to risk of AD differently in men and women.”The researchers found 11 different genes that produce varying levels of risk for, or protection against, Alzheimer’s disease in men and women.“These genes appear to have functions that are relevant to Alzheimer’s disease, including endocytosis and immunity,” Kunkle said. “These genes would not have been discovered in analyses that combine men and women, highlighting the importance of analyses that consider sex for novel gene discovery and precision medicine.”Four genes, in particular, caught the researchers’ attention, MCOLN3 and CHMP2B in men and CD1E and PTPRC in women.“MCOLN3 and CHMP2B regulate endocytosis,” Kunkle said, “the process whereby the cell cleans itself through transport of molecules for recycling or degradation. This process may reduce Alzheimer’s risk through reduction of buildup of amyloid and tau, two key Alzheimer disease proteins. CD1E and PTPRC are immune response genes, another known Alzheimer process. These genes could help refine biomarker and therapy development by providing gene targets that differentiate Alzheimer disease pathology in men and women.”The bottom line is this research supports the theory that the different risks for men and women for Alzheimer’s disease are gene-related.“This study strongly supports the hypothesis that some genetic factors contributing to AD are not identical for men and women,” Kunkle told BioSpace. “Understanding the different genetic landscape and risk profiles for Alzheimer disease between men and women provides information critical for precision medicine, helps refine targets for therapy, and improves diagnosis and prediction.”Source