Amyloid b interacts with the amyloid precursor protein: a potential toxic mechanism in Alzheimer's disease

• Published in: Nature neuroscience Vol. 3; no. 5; pp. 460 - 464
• Main Authors: Lorenzo, Alfredo, Yuan, Menglan, Zhang, Zhuohua, Paganetti, Paolo A, Sturchler-Pierrat, Christine, Staufenbiel, Matthias, Mautino, Jorge, Vigo, Francisco Sol, Sommer, Bernd, Yankner, Bruce A
• Format: Journal Article
• Language: English
• Published: 01-05-2000
• ISSN: 1097-6256
• DOI: 10.1038/74833

Amyloid b protein (Ab) deposition in the brain is a hallmark of Alzheimer's disease (AD). The fibrillar form of Ab is neurotoxic, although the mechanism of its toxicity is unknown. We showed that conversion of Ab to the fibrillar form markedly increased binding to specific neuronal membrane proteins, including amyloid precursor protein (APP). Nanomolar concentrations of fibrillar Ab bound cell-surface holo-APP in cortical neurons. Reduced vulnerability of cultured APP-null neurons to Ab neurotoxicity suggested that Ab neurotoxicity involves APP. Thus Ab toxicity may be mediated by the interaction of fibrillar Ab with neuronal membrane proteins, notably APP. An Ab-APP interaction reminiscent of the pathogenic mechanism of prions may thus contribute to neuronal degeneration in AD.