Dystrophic microglia are associated with neurodegenerative disease and not healthy aging in the human brain

Ryan K. Shahidehpour, Rebecca E. Higdon, Nicole G. Crawford, Janna H. Neltner, Eseosa T. Ighodaro, Ela Patel, Douglas Price, Peter T. Nelson, Adam D. Bachstetter

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Loss of physiological microglial function may increase the propagation of neurodegenerative diseases. Cellular senescence is a hallmark of aging; thus, we hypothesized age could be a cause of dystrophic microglia. Stereological counts were done for total microglia, two microglia morphologies (hypertrophic, and dystrophic) across the human lifespan. An age-associated increase in the number of dystrophic microglia was found in the hippocampus and frontal cortex. However, the increase in dystrophic microglia was proportional to the age-related increase in the total number of microglia. Thus, aging alone does not explain the presence of dystrophic microglia. We next tested if dystrophic microglia could be a disease-associated microglia morphology. Compared to controls, the number of dystrophic microglia was greater in cases with either Alzheimer's disease, dementia with Lewy bodies, or limbic-predominant age-related TDP-43 encephalopathy (LATE). These results demonstrate that microglia dystrophy, and not hypertrophic microglia, are the disease-associated microglia morphology. Finally, we found strong evidence for iron homeostasis changes in dystrophic microglia, providing a possible molecular mechanism driving the degeneration of microglia in neurodegenerative disease.

Original languageEnglish
Pages (from-to)19-27
Number of pages9
JournalNeurobiology of Aging
Volume99
DOIs
StatePublished - Mar 2021

Bibliographical note

Publisher Copyright:
© 2020 The Author(s)

Keywords

  • Aging
  • microglia morphology
  • neurodegeneration
  • neuroinflammation
  • neuropathology
  • senescence

ASJC Scopus subject areas

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Aging
  • General Neuroscience
  • Developmental Biology

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