DEGENERATION OF VASCULAR MUSCLE-CELLS IN CEREBRAL AMYLOID ANGIOPATHY OF ALZHEIMER-DISEASE

In cerebral amyloid angiopathy, the amyloid-beta (Abeta) deposits lie primarily in the tunica media suggesting that smooth muscle cells play an important role in Abeta deposition. To define this role, we conduc ted an immunocytochemical study of brain tissue from cases of Alzheime r disease with extensive cerebral amyloid angiopathy and cerebral hemo rrhage. Antibodies specific to recombinant beta protein precursor (bet aPP) and synthetic peptides homologous to various betaPP sequences fro m residue 18 to 689 of betaPP695 were used. Antibodies to actin, tropo myosin, alpha-actinin or desmin were used to label muscle cells. Antib odies to Abeta sequences intensely recognized the extracellular amyloi d deposit. Antibodies raised against betaPP sequences other than the A beta domain recognized smooth muscle cells. BetaPP-immunoreactivity wa s reduced in regions of Abeta deposits, since no muscle cells were rec ognized by cytoskeletal markers or observed ultrastructurally. In orde r to assess why Abeta is deposited in the tunica media, we used biotin -labelled PPP to determine if betaPP can be locally retained. We found betaPP bound to the tunica media of vessels but not other brain eleme nts. These findings suggest Abeta in blood vessels derives from degene rating betaPP-containing smooth muscle cells.