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

Amyloid b peptides Abs. of 39–43 amino acids constitute the major protein component of the amyloid plaques found in Alzheimer’s disease brain. The generation of Abs 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 Abs in Xenopus oocytes expressing rat brain RNA. The naturally occurring peptides Ab1–40 and Ab1–42 were both active, whereas the cytotoxic fragment Ab25–35 and the reverse peptide Ab40–1 did not stimulate the PI pathway. Abs rapidly lost potency in solution, suggesting that they were active only in their non-aggregated form. The Ab response was saturable and not reduced by a substance P antagonist. This pharmacology excludes the participation of known Ab binding proteins. The results indicate that a PI coupled receptor for non-aggregated Ab may be present in brain.