Amyloid β-peptide is produced by cultured cells during normal metabolism: A reprise

In the twenty years since George Glenner identified the amyloid beta-protein (Abeta), advances in understanding the biochemical pathology, genetics and cell biology of Alzheimer's disease have led to a detailed molecular hypothesis for the genesis of AD and brought us into human trials of anti-amyloid agents. The ability to study Abeta dynamically in cultured cells and in vivo derives from the recognition in 1992 that Abeta is a normal product of cellular metabolism throughout life and circulates as a soluble peptide in biological fluids. Here, I review the background underlying this discovery and then discuss its implications for research on Alzheimer's disease, particularly for the development of disease-modifying therapies.