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 conducted an immunocytochemical study of brain tissue from cases of Alzheimer disease with extensive cerebral amyloid angiopathy and cerebral hemorrhage. Antibodies specific to recombinant beta protein precursor (betaPP) and synthetic peptides homologous to various betaPP sequences from residue 18 to 689 of betaPP695 were used. Antibodies to actin, tropomyosin, alpha-actinin or desmin were used to label muscle cells. Antibodies to Abeta sequences intensely recognized the extracellular amyloid deposit. Antibodies raised against betaPP sequences other than the Abeta domain recognized smooth muscle cells. BetaPP-immunoreactivity was reduced in regions of Abeta deposits, since no muscle cells were recognized by cytoskeletal markers or observed ultrastructurally. In order 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 elements. These findings suggest Abeta in blood vessels derives from degenerating betaPP-containing smooth muscle cells.