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Acta Neuropathol Commun. 2015 May 23;3:32. doi: 10.1186/s40478-015-0209-z.

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

Author information

1
Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St, Lexington, KY, USA. adam.bachstetter@uky.edu.
2
Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St, Lexington, KY, USA.
3
Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA.
4
Department of Neurology, University of Kentucky, Lexington, KY, USA.
5
Department of Pathology and Laboratory Medicine, Division of Neuropathology, University of Kentucky, Lexington, KY, USA.
6
Department of Epidemiology, University of Kentucky, Lexington, KY, USA.
7
Department of Biostatistics, University of Kentucky, Lexington, KY, USA.
8
Department of Statistics, University of Kentucky, Lexington, KY, USA.

Abstract

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.

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.

PMID:
26001591
PMCID:
PMC4489160
DOI:
10.1186/s40478-015-0209-z
[Indexed for MEDLINE]
Free PMC Article

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