Coexistence of Alzheimer's amyloid precursor protein and amyloid protein in cerebral vessel walls.
Polyclonal antibodies to synthetic peptides homologous to amino acid residues 45-62, 597-624, and 676-695 of the predicted sequence of Alzheimer's amyloid precursor protein (APP) were used to investigate the site of origin of APP, and the relationship between APP and amyloid protein in Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D). Cortical sections as well as homogenates of isolated leptomeningeal and cortical microvessels from three patients with AD, two patients with HCHWA-D, and two nondemented controls were probed. In vessel extracts of both groups of patients and the controls, APP was detected as a set of proteins with electrophoretic mobility of 105 to 135 kilodaltons. In cortical sections of all subjects, APP immunoreactivity was found in leptomeningeal and cortical vessel walls. In patients with AD and HCHWA-D, APP and amyloid fibrils coexisted in the same vessels. Moreover, APP immunoreactivity was found in association with 50% of senile plaques in AD brains, but was not evidenced in parenchymal amyloid deposits in patients with HCHWA-D. These data suggest that the vascular system is a source of APP and that the processing of APP into insoluble fibrils in AD and HCHWA-D may take place in situ.
Tagliavini
F
F
Department of Pathology, New York University Medical Center, New York.
Ghiso
J
J
Timmers
W F
WF
Giaccone
G
G
Bugiani
O
O
Frangione
B
B
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor; D000686:Amyloidosis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D001808:Blood Vessels / Q000378:metabolism* / Q000648:ultrastructure; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D006801:Humans; D011498:Protein Precursors / Q000378:metabolism*
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D011498:Protein Precursors