Effects of 8-residue ? sheet breaker peptides on aged A?40-induced memory impairment and A?40 expression in rat brain and serum following intraamygdaloid injection.

Abstract

Amyloid?-protein (A?) assembly into toxic fibrillar structures is seminal in development of senile plaques, the pathological hallmark of Alzheimer's disease. Blocking this process could have a therapeutic value. ?-sheet breaker peptides (?SBP) decrease A? fibrillogenesis and neurotoxicity by preventing or dissolving misfolded A? aggregates. The present study investigated the effects of ?SBPs on A?40-related neuropathology, memory impairment in 8-armed radial maze and expression of A?40 in brain and serum. A?40 was injected into amygdaloid nucleus followed 8 days later by octapeptide?SBPs 15-22, 16-23 and 17-24. A?40 was detected not only in amygdala, but also in serum. A?40 induced cellular changes in amygdala and additionally in hippocampus. A?40 decreased correct choices, whereas increased errors (both number of arms revisited and total number of revisits) and latency of completing the maze test. The ?SBPs decreased A?40-induced pathological changes, memory impairment and A?40 expression in serum. The ?SBP15-22 distinctively decreased the total errors on day 14. The present results show that octapeptide ?SBPs corrected A?40-induced memory impairment, and support investigation of ?SBPs as a promising treatment of diseases characterized by neurodegeneration and memory impairment such as Alzheimer's disease.