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

Abstract

Introduction: Higher brain tocopherol levels have been associated with lower levels of Alzheimer's disease (AD) neuropathology; however, the underlying mechanisms are unclear.

Methods: We studied the relations of α- and γ-tocopherol brain levels to microglia density in 113 deceased participants from the Memory and Aging Project. We used linear regression analyses to examine associations between tocopherol levels and microglia densities in a basic model adjusted for age, sex, education, apolipoprotein E (APOE)ε4 genotype (any ε4 allele vs. none) , and post-mortem time interval, and a second model additionally adjusted for total amyloid load and neurofibrillary tangle severity.

Results: Higher α- and γ-tocopherol levels were associated with lower total and activated microglia density in cortical but not in subcortical brain regions. The association between cortical α-tocopherol and total microglia density remained statistically significant after adjusting for AD neuropathology.

Discussion: These results suggest that the relation between tocopherols and AD might be partly explained by the alleviating effects of tocopherols on microglia activation.

Keywords: amyloid; antioxidants; anti‐inflammatory; cerebral cortex; glial cells; inflammation; microglia; nutrition; pathology; tau; tocopherols; vitamin E.

FIGURE 1

Representative photograph of microglial morphological states in the inferior temporal cortex. Scale bars are 10 µm

FIGURE 2

Associations of brain tocopherol levels with microglia density. The standardized effect estimates on microglia density of brain tocopherols adjusted for age, sex, education, post‐mortem time interval, and APOEε4 genotype (any ε4 allele vs. none) are shown. The estimates are shown for α‐tocopherol (circles) and γ‐tocopherol (diamonds) by region (cortical = yellow, subcortical = green). Point estimates are shown as boxes with whiskers denoting the 95% confidence interval of the effect estimates. SD, standard deviation

FIGURE 3

Scatterplots of the associations of α‐tocopherol levels with microglia density. The upper graphs in dark blue depict the associations in the cortical brain regions, whereas the lower graphs in light blue depict the associations in the subcortical brain regions. Microglia density and α‐tocopherol levels are shown as log‐transformed z‐scores