title: High-definition characterization of cerebral β-amyloid angiopathy in Alzheimer's disease.
abstract: The occurrence and progression of cerebral β-amyloid angiopathy and β-amyloid plaques in sporadic Alzheimer's disease may be attributed to aging-related deficiencies in β-amyloid drainage along cerebral perivascular pathways. To elucidate high-definition characteristics of cerebral β-amyloid deposition, we performed immunogold silver staining for β-amyloid-40 and β-amyloid-42 on semithin LR White-embedded tissue sections from 7 Alzheimer's disease/severe cerebral β-amyloid angiopathy, 9 Alzheimer's disease/mild cerebral β-amyloid angiopathy, 5 old control, and 4 young control autopsy brains. In vessel walls, β-amyloid-40 and β-amyloid-42 deposits were unevenly distributed along the adventitia and among the medial smooth muscle cells. β-Amyloid-40 immunoreactivity appeared greater than that of β-amyloid-42 in vessel walls, with β-amyloid-42 being preferentially located on their abluminal regions. In capillary walls, either β-amyloid-40 or β-amyloid-42 deposits or both were present in 6 of 7 severe cerebral β-amyloid angiopathy and in 1 of 9 mild cerebral β-amyloid angiopathy cases, with a marked variation in thickness and focally abluminal excrescences. In 5 of 7 severe cerebral β-amyloid angiopathy cases, a subset of β-amyloid-laden capillaries revealed either β-amyloid-40 or β-amyloid-42 deposits or both radiating from their walls into the surrounding neuropil ("pericapillary deposits"). No vascular β-amyloid-40 or β-amyloid-42 deposits were observed in any of the controls. In conclusion, the patterns of β-amyloid-42 and β-amyloid-40 immunoreactivity in vessel walls suggest that β-amyloid deposits occur in the vascular basement membranes along cerebral perivascular drainage pathways, extending from cortical capillaries to leptomeningeal arteries. The presence of pericapillary β-amyloid deposits suggests that a subset of β-amyloid plaques originate from β-amyloid-laden capillaries, particularly in Alzheimer's disease brains that exhibit preferential capillary involvement by cerebral β-amyloid angiopathy.
authors.affiliation: Department of Pathology and Laboratory Medicine (Neuropathology), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. vsoontor@ucsd.edu
authors.forename: Virawudh
authors.initials: V
authors.lastname: Soontornniyomkij
authors.forename: Cecilia
authors.initials: C
authors.lastname: Choi
authors.forename: Justine
authors.initials: J
authors.lastname: Pomakian
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000098:blood supply; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism*; D013194:Staining and Labeling; D055815:Young Adult
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)