title: Disease-related microglia heterogeneity in the hippocampus of Alzheimer's disease, dementia with Lewy bodies, and hippocampal sclerosis of aging.
abstract: BACKGROUND
  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.
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St, Lexington, KY, USA. adam.bachstetter@uky.edu.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Bachstetter
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St, Lexington, KY, USA.|Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Van Eldik
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St, Lexington, KY, USA.|Department of Neurology, University of Kentucky, Lexington, KY, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St, Lexington, KY, USA.|Department of Pathology and Laboratory Medicine, Division of Neuropathology, University of Kentucky, Lexington, KY, USA.
authors.forename: Janna H
authors.initials: JH
authors.lastname: Neltner
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St, Lexington, KY, USA.|Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA.
authors.forename: Eseosa T
authors.initials: ET
authors.lastname: Ighodaro
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St, Lexington, KY, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Webster
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St, Lexington, KY, USA.
authors.forename: Ela
authors.initials: E
authors.lastname: Patel
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St, Lexington, KY, USA.|Department of Epidemiology, University of Kentucky, Lexington, KY, USA.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Abner
authors.affiliation: Department of Biostatistics, University of Kentucky, Lexington, KY, USA.|Department of Statistics, University of Kentucky, Lexington, KY, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kryscio
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St, Lexington, KY, USA.|Department of Pathology and Laboratory Medicine, Division of Neuropathology, University of Kentucky, Lexington, KY, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000473:pathology; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001344:Autopsy; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D003704:Dementia / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D020961:Lewy Body Disease / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D012598:Sclerosis / Q000473:pathology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; C112986:AIF1 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule