Alzheimer's disease and β-amyloid

To the Editor: The report by Yankner and Mesulam (Dec. 26 issue)¹ on β-amyloid and the pathogenesis of Alzheimer's disease is a timely and comprehensive presentation of the fascinating genetics and protein biochemistry of this common, devastating illness. However, some modification of their hypothesis for the mechanism of neuronal degeneration should be considered. According to the authors, the ability of the β-amyloid peptide to bind the cellular receptors required to clear the serpin protease inhibitor—enzyme complexes² could result in long-term proteolytic damage from the uncleared proteases and may be a direct cause of neuronal degeneration in Alzheimer's disease. This interpretation.