Association Between Hippocampal Microglia, AD and LATE-NC, and Cognitive Decline in Older Adults

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2024 Mar 18

PMID 38494787

Authors

Alifiya Kapasi

Lei Yu

Sue E Leurgans

Sonal Agrawal

Patricia A Boyle

David A Bennett

Julie A Schneider

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Hippocampal neuronal loss and cognitive decline in LATE-NC and ADNC among community-dwelling older persons.

Agrawal S, Yu L, Leurgans S, Nag S, Barnes L, Bennett D Alzheimers Dement. 2025; 21(2):e14500.

PMID: 39888320 PMC: 11851160. DOI: 10.1002/alz.14500.

Co-Aggregation of TDP-43 with Other Pathogenic Proteins and Their Co-Pathologies in Neurodegenerative Diseases.

Jiang L, Zhang X, Hu H Int J Mol Sci. 2024; 25(22).

PMID: 39596445 PMC: 11594478. DOI: 10.3390/ijms252212380.

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

Kapasi A, Yu L, Leurgans S, Agrawal S, Boyle P, Bennett D Alzheimers Dement. 2024; 20(5):3193-3202.

PMID: 38494787 PMC: 11095444. DOI: 10.1002/alz.13780.

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