Open AccessGeneration of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells.
Author(s) -
Jorge Busciglio,
Dana Gabuzda,
Paul Matsudaira,
Bruce A. Yankner
Publication year - 1993
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.90.5.2092
Subject(s) - p3 peptide , amyloid precursor protein , amyloid (mycology) , biochemistry of alzheimer's disease , secretion , secretory pathway , amyloid beta , biochemistry , beta (programming language) , peptide , microbiology and biotechnology , biology , protein precursor , golgi apparatus , chemistry , alzheimer's disease , cell , enzyme , medicine , disease , botany , computer science , programming language
The cellular mechanism underlying the generation of beta-amyloid in Alzheimer disease and its relationship to the normal metabolism of the amyloid precursor protein are unknown. In this report, we show that 3- and 4-kDa peptides derived from amyloid precursor protein are normally secreted. Epitope mapping and radiolabel sequence analysis suggest that the 4-kDa peptide is closely related to full-length beta-amyloid and the 3-kDa species is a heterogeneous set of peptides truncated at the beta-amyloid N terminus. The beta-amyloid peptides are secreted in parallel with amyloid precursor protein. Inhibitors of Golgi processing inhibit secretion of beta-amyloid peptides, whereas lysosomal inhibitors have no effect. The secretion of beta-amyloid-related peptides occurs in a wide variety of cell types, but which peptides are produced and their absolute levels are dependent on cell type. Human astrocytes generated higher levels of beta-amyloid than any other cell type examined. These results suggest that beta-amyloid is generated in the secretory pathway and provide evidence that glial cells are a major source of beta-amyloid production in the brain.