RAPID CELLULAR UPTAKE OF ALZHEIMER AMYLOID BETA-A4 PEPTIDE BY CULTURED HUMAN NEUROBLASTOMA-CELLS

Cerebral deposition of beta A4 (beta-amyloid) peptide is a major patho logical feature of Alzheimer's disease, Although the mechanism of beta A4 production from cells has been investigated extensively, so far li ttle is known about the catabolism of the peptide, We report here that the human neuroblastoma cell line SH-SY5Y can rapidly clear beta A4 i n the culture medium, The clearance was not due to the degradation by extracellularly released protease, but rather due to intracellular deg radation after cellular uptake, This clearance activity was specific t o SH-SY5Y cells among several cell types examined. Some of the beta A4 -derived peptides lacking the N-terminal part of the molecule were not catabolized, suggesting a specific interaction between the cells and beta A4, Although most of the peptide was degraded after uptake, small amounts of peptide was accumulated in insoluble fractions of the cell s and remained stable for several days, These observations suggest tha t this uptake-degradation activity may contribute to AD pathogenesis i n two different ways: either to prevent the amyloid deposition by redu cing extracellular beta A4 concentrations, or to promote the depositio n by producing insoluble seeds for amyloid formation.