Introduction: This study investigates the relationship between microglia inflammation in the hippocampus, brain pathologies, and cognitive decline.
Methods: Participants underwent annual clinical evaluations and agreed to brain donation. Neuropathologic evaluations quantified microglial burden in the hippocampus, amyloid beta (Aβ), tau tangles, and limbic age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy neuropathologic changes (LATE-NC), and other common brain pathologies. Mixed-effect and linear regression models examined the association of microglia with a decline in global and domain-specific cognitive measures, and separately with brain pathologies. Path analyses estimated direct and indirect effects of microglia on global cognition.
Result: Hippocampal microglia were associated with a faster decline in global cognition, specifically in episodic memory, semantic memory, and perceptual speed. Tau tangles and LATE-NC were independently associated with microglia. Other pathologies, including Aβ, were not related. Regional hippocampal burden of tau tangles and TDP-43 accounted for half of the association of microglia with cognitive decline.
Discussion: Microglia inflammation in the hippocampus contributes to cognitive decline. Tau tangles and LATE-NC partially mediate this association.
Keywords: Alzheimer's disease; LATE-NC; cognitive decline; hippocampal microglia.
© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.