Brain tocopherol levels are associated with lower activated microglia density in elderly human cortex

Background Higher intake of vitamin E has been associated with a lower risk of Alzheimer’s disease (AD), however the underlying mechanisms are unclear. One explanation might be that anti‐inflammatory properties of tocopherols prevent microglia activation. In this study we investigated the association of brain tocopherol levels with microglia activation in elderly humans. Method We included 113 deceased participants (88.5±6 years, 60% female) from the prospective Memory and Aging Project. Brain levels of α‐ and γ‐tocopherol were measured by HPLC coupled to electrochemical detection. Microglia presence was assessed in three stages of activation, based on morphology; i.e. I – not activated, II – activated, III – most activated. Microglia densities and tocopherol levels were log‐transformed when not normally distributed, standardized and averaged across two cortical and two subcortical brain regions. Linear regression analyses examined associations between tocopherol levels and microglia densities (outcome) in two models; a model adjusted for age, sex, education, APOE ε4 genotype and post mortem time interval (model 1), and a model additionally adjusted for total amyloid load and neurofibrillary tangles severity (model 2). Result Total microglia density (stage I‐III) was lower in cortical versus subcortical brain regions (153.2 (111.2‐194.0); 209.2 (175.8‐224.1), p