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: Virawudh Soontornniyomkij, Cecilia Choi, Justine Pomakian, Harry V Vinters
• Journal: Human pathology (Hum Pathol) Vol. 41 Issue 11 Pg. 1601-8 (Nov 2010) ISSN: 1532-8392 [Electronic] United States
• PMID: 20688356 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Peptide Fragments
• amyloid beta-protein (1-40)
• amyloid beta-protein (1-42)

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Alzheimer Disease (metabolism, pathology)
• Amyloid beta-Peptides (metabolism)
• Brain (blood supply)
• Capillaries (metabolism, pathology)
• Cerebral Amyloid Angiopathy (metabolism, pathology)
• Female
• Humans
• Male
• Middle Aged
• Muscle, Smooth, Vascular (metabolism, pathology)
• Peptide Fragments (metabolism)
• Staining and Labeling
• Young Adult