Amyloid beta-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. beta-sheet breaker peptides (beta SBP) decrease A beta fibrillogenesis and neurotoxicity by preventing or dissolving misfolded A beta aggregates. The present study investigated the effects of beta SBPs on A beta 40-related neuropathology, memory impairment in 8-armed radial maze and expression of A beta 40 in brain and serum. A beta 40 was injected into amygdaloid nucleus followed 8 days later by octapeptide beta SBPs 15-22, 16-23 and 17-24. A beta 40 was detected not only in amygdala, but also in serum. A beta 40 induced cellular changes in amygdala and additionally in hippocampus. A beta 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 beta SBPs decreased A beta 40-induced pathological changes, memory impairment and A beta 40 expression in serum. The beta SBP15-22 distinctively decreased the total errors on day 14. The present results show that octapeptide beta SBPs corrected A beta 40-induced memory impairment, and support investigation of beta SBPs as a promising treatment of diseases characterized by neurodegeneration and memory impairment such as Alzheimer's disease
