Dystrophic Microglia Are Associated with Neurodegenerative Disease and not Healthy Aging in the Human Brain

Authors

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

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 performed for total microglia, 2 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 with 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. 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.

Document Type

Article

Publication Date

1-7-2021

Notes/Citation Information

Published in Neurobiology of Aging, v. 99.

© 2020 The Author(s)

This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.neurobiolaging.2020.12.003

Funding Information

Research reported in this publication was supported by the National Institutes of Health under award numbers P30 AG028383, R35 GM124977, and R21AG066865.

Repository Citation

Shahidehpour, Ryan K.; Higdon, Rebecca E.; Crawford, Nicole G.; Neltner, Janna H.; Ighodaro, Eseosa T.; Patel, Ela; Price, Douglas; Nelson, Peter T.; and Bachstetter, Adam D., "Dystrophic Microglia Are Associated with Neurodegenerative Disease and not Healthy Aging in the Human Brain" (2021). Spinal Cord and Brain Injury Research Center Faculty Publications. 34.
https://uknowledge.uky.edu/scobirc_facpub/34