Amyloid β peptides activate the phosphoinositide signaling pathway in oocytes expressing rat brain RNA

Amyloid β peptides (Aβs) of 39-43 amino acids constitute the major protein component of the amyloid plaques found in Alzheimer's disease brain. The generation of Aβs is regulated by the phosphoinositide (PI) pathway, which commonly couples to transmitter receptors. This study reports evidence for the activation of the PI pathway by Aβs in Xenopus oocytes expressing rat brain RNA. The naturally occurring peptides Aβ1-40 and Aβ1-42 were both active, whereas the cytotoxic fragment Aβ25-35 and the reverse peptide Aβ40-1 did not stimulate the PI pathway. Aβs rapidly lost potency in solution, suggesting that they were active only in their non-aggregated form. The Aβ response was saturable and not reduced by a substance P antagonist. This pharmacology excludes the participation of known Aβ binding proteins. The results indicate that a PI coupled receptor for non-aggregated Aβ may be present in brain. Copyright (C) 2000 Elsevier Science B.V.