The peptide sequence Arg-Glu-Arg, present in the amyloid precursor protein, protects against memory loss caused by Aβ and acts as a cognitive enhancer

Amino acid sequences containing the palindromic tripeptide RER, matching amino acids 328-330 of the amyloid precursor protein APP, when injected intracerebrally prior to or just after training, protect against memory loss induced by amyloid-beta (Aβ) in a one-trial passive avoidance task in the young chick. RER also acts as a cognitive enhancer, strengthening memory for a weak version of the task. N-terminal acylation of RER protects it against rapid degradation, and Ac-RER is effective in restoring memory if administered peripherally. Biotinylated RER binds to chick neuronal perikarya in an APP-displaceable manner via 66 and ~110 kDa neuronal cell membrane proteins. We suggest that RER binding is likely to exert effects on memory retention via receptor-mediated events that include activation of second messenger pathways. These findings suggest that RER and its derivatives may offer a novel approach to enhancing the neuroprotective effects of APP and alleviating the effects of memory loss in the early stages of Alzheimer’s disease