The effects of human leukocyte antigen DRB1*13 and apolipoprotein E on age-related variability of synchronous neural interactions in healthy women

Background: Age-related brain changes are well-documented and influenced by genetics. Extensive research links apolipoprotein E (apoE) to brain function, with the E4 allele serving as a risk factor for brain disease, including Alzheimer's disease, and the E2 allele conferring protection. Recent evidence also supports protective effects of another gene, human leukocyte antigen (HLA) DRB1*13, on brain disease and age-related brain atrophy in cognitively healthy adults. Here we investigated the effects of apoE and HLA DRB1*13 on brain function by examining changes in neural network properties with age in healthy adults. Methods: One hundred seventy-eight cognitively healthy women (28–99 y old) underwent a magnetoencephalography scan and provided a blood sample for genetic analysis. Age-related changes in neural network variability in genetic subgroups of DRB1*13 × apoE genotype combinations were assessed using linear regression of network variability against age. Findings: For individuals lacking a DRB1*13 allele and/or carrying an apoE4 allele, network variability increased significantly with age. In contrast, no such increase was observed in the presence of DRB1*13 and/or apoE2. Interpretation: These findings extend previous research documenting the protective effect of DRB1*13 on brain structure to include protection against age-related changes in brain function, and demonstrate similar protective effects on neural network variability for either DRB1*13 or apoE2. These protective effects could be due to reduction or elimination of factors known to disrupt brain function, including neuroinflammation and amyloid beta protein. Funding: U.S. Department of Veterans Affairs, and University of Minnesota.