Disease-related microglia heterogeneity in the hippocampus of Alzheimer's disease, dementia with Lewy bodies, and hippocampal sclerosis of aging

Adam D. Bachstetter, Linda J. Van Eldik, Frederick A. Schmitt, Janna H. Neltner, Eseosa T. Ighodaro, Scott J. Webster, Ela Patel, Erin L. Abner, Richard J. Kryscio, Peter T. Nelson

Research output: Contribution to journalArticlepeer-review

138 Scopus citations

Abstract

RESULTS: Here we studied cases with pathologically-confirmed AD (n = 7), HS-Aging (n = 7), AD + HS-aging (n = 4), DLB (n = 12), and normal (cognitively intact) controls (NC) (n = 9) from the University of Kentucky Alzheimer's Disease Center autopsy cohort. We defined five microglia morphological phenotypes in the autopsy samples: ramified, hypertrophic, dystrophic, rod-shaped, and amoeboid. The Aperio ScanScope digital neuropathological tool was used along with two well-known microglial markers: IBA1 (a marker for both resting and activated microglia) and CD68 (a lysosomal marker in macrophages/microglia associated with phagocytic cells). Hippocampal staining analyses included studies of subregions within the hippocampal formation and nearby white matter. Using these tools and methods, we describe variation in microglial characteristics that show some degree of disease specificity, including, (1) increased microglia density and number in HS-aging and AD + HS-aging; (2) low microglia density in DLB; (3) increased number of dystrophic microglia in HS-aging; and (4) increased proportion of dystrophic to all microglia in DLB.

CONCLUSIONS: We conclude that variations in morphologies among microglial cells, and cells of macrophage lineage, can help guide future work connecting neuroinflammatory mechanisms with specific neurodegenerative disease subtypes.

INTRODUCTION: Neuropathological, genetic, and biochemical studies have provided support for the hypothesis that microglia participate in Alzheimer's disease (AD) pathogenesis. Despite the extensive characterization of AD microglia, there are still many unanswered questions, and little is known about microglial morphology in other common forms of age-related dementia: particularly, dementia with Lewy bodies (DLB) and hippocampal sclerosis of aging (HS-Aging). In addition, no prior studies have attempted to compare and contrast the microglia morphology in the hippocampus of various neurodegenerative conditions.

Original languageEnglish
Pages (from-to)32
Number of pages1
JournalActa neuropathologica communications
Volume3
DOIs
StatePublished - May 23 2015

Bibliographical note

Funding Information:
We are profoundly grateful to all of the study participants who make this research possible. The corresponding author, Adam Bachstetter, PhD, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Research reported in this publication was supported by National Institutes of Health under award numbers P30 AG028383, K99 AG044445. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health.

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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