High-definition characterization of cerebral β-amyloid angiopathy in Alzheimer's disease

The occurrence and progression of cerebral beta-amyloid angiopathy and beta-amyloid plaques in sporadic Alzheimer's disease may be attributed to aging-related deficiencies in beta-amyloid drainage along cerebral perivascular pathways. To elucidate high-definition characteristics of cerebral beta-amyloid deposition, we performed immunogold silver staining for beta-amyloid-40 and beta-amyloid-42 on semithin LR White-embedded tissue sections from 7 Alzheimer's disease/severe cerebral beta-amyloid angiopathy, 9 Alzheimer's disease/mild cerebral beta-amyloid angiopathy, 5 old control, and 4 young control autopsy brains. In vessel walls, beta-amyloid-40 and beta-amyloid-42 deposits were unevenly distributed along the adventitia and among the medial smooth muscle cells. beta-Amyloid-40 immunoreactivity appeared greater than that of beta-amyloid-42 in vessel walls, with beta-amyloid-42 being preferentially located on their abluminal regions. In capillary walls, either beta-amyloid-40 or beta-amyloid-42 deposits or both were present in 6 of 7 severe cerebral beta-amyloid angiopathy and in 1 of 9 mild cerebral beta-amyloid angiopathy cases, with a marked variation in thickness and focally abluminal excrescences. In 5 of 7 severe cerebral beta-amyloid angiopathy cases, a subset of beta-amyloid-laden capillaries revealed either beta-amyloid-40 or beta-amyloid-42 deposits or both radiating from their walls into the surrounding neuropil ("pericapillary deposits"). No vascular beta-amyloid-40 or beta-amyloid-42 deposits were observed in any of the controls. In conclusion, the patterns of beta-amyloid-42 and beta-amyloid-40 immunoreactivity in vessel walls suggest that beta-amyloid deposits occur in the vascular basement membranes along cerebral perivascular drainage pathways, extending from cortical capillaries to leptomeningeal arteries. The presence of pericapillary beta-amyloid deposits suggests that a subset of beta-amyloid plaques originate from beta-amyloid-laden capillaries, particularly in Alzheimer's disease brains that exhibit preferential capillary involvement by cerebral beta-amyloid angiopathy. (C) 2010 Elsevier Inc. All rights reserved.