Cerebrovascular amyloidosis: Experimental analysis in vitro and in vivo

With advancing age, the likelihood of beta-amyloid deposition in the cerebr al vasculature increases, particularly in individuals with Alzheimer's dise ase. The beta-amyloid typically accumulates in the basal lamina of the arte riolar tunica media, and frequently extends into the adjacent neuropil. Cer ebrovascular B-amyloid increases the risk of hemorrhagic stroke, and may al so play a role in the pathogenesis of AD. Genetic variations have been iden tified that are causative or risk factors for cerebrovascular B-amyloid, in cluding particular mutations in the genes for beta-amyloid precursor protei n, presenilins 1 and 2, and possibly cystatin C, as well as polymorphisms i n apolipoprotein E. Cerebrovascular amyloidosis is now being studied in a v ariety of in vitro and in vivo models, including cultured vascular smooth m uscle cells, transgenic mice, and aged animals such as nonhuman primates. M ethods for delivering agents selectively to vascular amyloid in living subj ects are now being developed, and these techniques are paving the way to th e development of diagnostic tools and therapies for cerebrovascular amyloid osis.