PROGRESSION OF CEREBRAL AMYLOID ANGIOPATHY - ACCUMULATION OF AMYLOID-BETA-40 IN AFFECTED VESSELS

Cerebrovascular deposits of amyloid (cerebral amyloid angiopathy, or C AA) are generally asymptomatic, but in advanced cases, they can lead t o 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 hemorrha ge (''severe CAA''). Cortical and meningeal vessels were immunostained for beta-amyloid and examined by confocal microscopy and by systemati c quantitative sampling. We focused on 2 quantitative parameters: the proportion of vessels affected by amyloid (a measure of amyloid seedin g 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 sever e CAA (0.29 vs 0.32, p = 0.65), but rather an increase in the area of the 40 amino acid form of beta-amyloid per affected cortical vessel (1 98.5 +/- 38.7 vs 455.8 +/- 100.9 mu m(2)/vessel, p < 0.007). Increasin g doses (from 0 to 1 to 2 copies) of the apolipoprotein E epsilon 4 al lele were also associated with greater amyloid per vessel without chan ge in the proportion of affected vessels within each class of CAA seve rity. These findings suggest that progression from asymptomatic to adv anced CAA reflects progressive accumulation of amyloid in vessels prev iously seeded with amyloid, and that this process is selectively enhan ced by apolipoprotein E epsilon 4.