Progression of Cerebral Amyloid Angiopathy: Accumulation of Amyloid-ß40 in Affected Vessels

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Abstract

Abstract.

Cerebrovascular deposits of amyloid (cerebral amyloid angiopathy, or CAA) are generally asymptomatic, but in advanced cases, they can lead to vessel rupture and hemorrhage. The process of progression in CAA was studied by comparison of postmortem brains with asymptomatic (“mild”) CAA to brains with the form of the disease associated with hemorrhage (“severe CAA”). Cortical and meningeal vessels were immunostained for β-amyloid and examined by confocal microscopy and by systematic quantitive sampling. We focused on 2 quantitative parameters: the proportion of vessels affected by amyloid (a measure of amyloid seeding of vessels) and the amount of amyloid per affected vessel (a measure of growth of existing lesions). Surprisingly, there was no difference between the proportion of affected cortical vessels in mild and severe CAA (0.29 vs 0.32, p = 0.65), but rather an increase in the area of the 40 amino acid form of β-amyloid per affected cortical vessel (198.5 ± 38.7 vs 455.8 ± 100.9 µm2/vessel, p < 0.007). Increasing doses (from 0 to 1 to 2 copies) of the apolipoprotein E ε4 allele were also associated with greater amyloid per vessel without change in the proportion of affected vessles within each class of CAA severity. These findings suggest that progression from asymptomatic to advanced CAA reflects progressive accumulation of amyloid in vessels previously seeded with amyloid, and that this process is selectively enhanced by apoliporprotein E ε4.

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