Association between APOE genotype and microglial cell morphology.

Autor: Kloske CM; Department of Physiology, College of Medicine, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA., Gearon MD; Sanders-Brown Center on Aging, College of Medicine, University of Kentucky, Lexington, Kentucky, USA., Weekman EM; Department of Physiology, College of Medicine, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA., Rogers C; Sanders-Brown Center on Aging, College of Medicine, University of Kentucky, Lexington, Kentucky, USA., Patel E; Sanders-Brown Center on Aging, College of Medicine, University of Kentucky, Lexington, Kentucky, USA., Bachstetter A; Department of Neuroscience, College of Medicine, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA., Nelson PT; Department of Pathology and Laboratory Medicine, College of Medicine, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA., Wilcock DM; Department of Physiology, College of Medicine, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
Jazyk: angličtina
Zdroj: Journal of neuropathology and experimental neurology [J Neuropathol Exp Neurol] 2023 Jun 20; Vol. 82 (7), pp. 620-630.
DOI: 10.1093/jnen/nlad031
Abstrakt: APOE is the largest genetic risk factor for late-onset Alzheimer disease (AD) with E4 conferring an increased risk for AD compared to E3. The ApoE protein can impact diverse pathways in the brain including neuroinflammation but the precise impact of ApoE isoforms on inflammation remains unknown. As microglia are a primary source of neuroinflammation, this study determined whether ApoE isoforms have an impact on microglial morphology and activation using immunohistochemistry and digital analyses. Analysis of ionized calcium-binding adaptor molecule 1 (Iba1) immunoreactivity indicated greater microglial activation in both the hippocampus and superior and middle temporal gyrus (SMTG) in dementia participants versus non-demented controls. Further, only an increase in activation was seen in E3-Dementia participants in the entire SMTG, whereas in the grey matter of the SMTG, only a diagnosis of dementia impacted activation. Specific microglial morphologies showed a reduction in ramified microglia in the dementia group. For rod microglia, a reduction was seen in E4-Control patients in the hippocampus whereas in the SMTG an increase was seen in E4-Dementia patients. These findings suggest an association between ApoE isoforms and microglial morphologies and highlight the importance of considering ApoE isoforms in studies of AD pathology.
(© The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze: MEDLINE