Identification of a stable fragment of the Alzheimer amyloid precursor containing the beta-protein in brain microvessels.

摘要: Altered proteolysis of the beta-amyloid precursor protein (beta APP) resulting in release approximately 40-residue amyloid beta-protein (A beta P) may be a seminal pathogenetic event Alzheimer disease. Using region-specific APP antibodies, we searched for stable proteolytic intermediates containing intact A P region brain tissue. 22-kDa fragment was selectively detected microvessels purified from cerebral cortex and other regions. On immunoblots, band is labeled by five distinct antisera to carboxyl-terminal peptides affinity-purified antibodies recombinant proteins APP444-592 APP592-695, which flank region. The virtually undetectable whole-brain homogenates or microvessel-free fractions brain. extractable Triton X-100 detergents, indicating its membrane association. In comparison with cortical microvessels, white matter, cerebellum, nonneural tissues contain lower amounts protein. found both normal disease brains occurs low fresh bovine size specific immunoreactivity indicate that it P. occurrence this potentially amyloidogenic intermediate consistent vascular hematogenous origin some deposits