EXPERIMENTAL DEPOSITION OF ALZHEIMER AMYLOID BETA-PROTEIN IN CANINE LEPTOMENINGEAL VESSELS

To study the pathogenesis of cerebral amyloid angiopathy (CAA), organ cultures of canine leptomeninges were incubated with fluorescein-conju gated amyloid beta-protein (FA beta, residues 1-40; 10 nM to 200 mu M) . Fluorescence microscopy showed focal and dose-dependent FA beta bind ing to blood vessels affected by CAA at FA beta-concentrations as low as 10 nM. The new A beta deposits appeared to be extracellular and wer e localized to the middle and outer layers of leptomeningeal arteriole s. FA Rho partially co-locaiized with apolipoprotein E (ApoE) as revea led by confocal microscopy, suggesting that A beta in situ binds to Ap oE. Young dogs or old dogs without CAA showed no deposition of FA beta . Our results indicate that after initiation of CAA pathology, physiol ogical concentrations of soluble A beta are sufficient to sustain its further deposition and therefore the progression of CAA.