Association between hippocampal microglia, AD and LATE-NC, and cognitive decline in older adults

Alzheimers Dement. 2024 May;20(5):3193-3202. doi: 10.1002/alz.13780. Epub 2024 Mar 17.


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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Cognitive Dysfunction* / pathology
  • DNA-Binding Proteins / metabolism
  • Female
  • Hippocampus* / pathology
  • Humans
  • Male
  • Microglia* / pathology
  • Neuropsychological Tests / statistics & numerical data
  • tau Proteins / metabolism