Rapid cellular uptake of Alzheimer amyloid βA4 peptide by cultured human neuroblastoma cells

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Abstract
Cerebral deposition of βA4 (β‐amyloid) peptide is a major pathological feature of Alzheimer's disease. Although the mechanism of βA4 production from cells has been investigated extensively, so far little is known about the catabolism of the peptide. We report here that the human neuroblastoma cell line SH‐SY5Y can rapidly clear βA4 in the culture medium. The clearance was not due to the degradation by extracellularly released protease, but rather due to intracellular degradation after cellular uptake. This clearance activity was specific to SH‐SY5Y cells among several cell types examined. Some of the βA4‐derived peptides lacking the N‐terminal part of the molecule were not catabolized, suggesting a specific interaction between the cells and βA4. Although most of the peptide was degraded after uptake, small amounts of peptide was accumulated in insoluble fractions of the cells and remained stable for several days. These observations suggest that this uptake‐degradation activity may contribute to AD pathogenesis in two different ways: either to prevent the amyloid deposition by reducing extracellular βA4 concentrations, or to promote the deposition by producing insoluble seeds for amyloid formation.