Apolipoprotein D is a component of compact but not diffuse amyloid-beta plaques in Alzheimer's disease temporal cortex.
Apolipoprotein D (apoD) is elevated in Alzheimer's disease (AD) cortex, localizing to cells, blood vessels, and neuropil deposits (plaques). The role of apoD in AD pathology and the extent of its co-distribution with diffuse (amorphous) and compact (dense fibrillar) amyloid-beta (Abeta) plaques are currently unclear. To address this issue, we combined apoD and Abeta immunohistochemistry with ThioS/X-34 staining of the beta-pleated sheet protein conformation in temporal cortex from 36 AD patients and 12 non-demented controls. ApoD-immunoreactive, Abeta-immunoreactive, and ThioS/X-34-stained plaques were detected exclusively in AD tissue. Dual-immunolabeling showed that 63% of Abeta plaques co-localized apoD. All apoD plaques contained Abeta protein and ThioS/X-34 fluorescence. Compared to controls, AD cases showed elevated vascular and intracellular apoD immunostaining which localized primarily to cells clustered within plaques and around large blood vessels. ApoD-immunoreactive cells within plaques morphologically matched MHC-II- and CD-68-immunoreactive microglia, and did not contain the astrocytic marker GFAP, which labeled a subset of apoD-immunoreactive cells surrounding plaques. These data suggest that neuropil deposits of apoD localize only to a subset of Abeta plaques, which contain compact aggregates of fibrillar Abeta. Elevated apoD in AD brain may influence Abeta aggregation, or facilitate phagocytosis and transport of Abeta fibrils from plaques to cerebral vasculature.
Desai
Purnima P
PP
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Ikonomovic
Milos D
MD
Abrahamson
Eric E
EE
Hamilton
Ronald L
RL
Isanski
Barbara A
BA
Hope
Caroline E
CE
Klunk
William E
WE
DeKosky
Steven T
ST
Kamboh
M Ilyas
MI
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001053:Apolipoproteins / Q000378:metabolism*; D053399:Apolipoproteins D; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D005456:Fluorescent Dyes; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D019581:Neuropil / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D017433:Protein Structure, Secondary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000097382:CD68 Molecule
D016229:Amyloid beta-Peptides; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001053:Apolipoproteins; D053399:Apolipoproteins D; D005456:Fluorescent Dyes; D000949:Histocompatibility Antigens Class II; C067980:CD68 antigen, human; D000097382:CD68 Molecule