Mileusnic, Radmila; Lancashire, Christine L. and Rose, Steven P.R.
Amyloid precursor protein: from synaptic plasticity to Alzheimer’s disease.
Annals of the New York Academy of Sciences, 1048(1) pp. 149–165.
The amyloid precursor protein (APP) has been shown to be implicated in age-associated plastic changes at synapses that might contribute to memory loss in Alzheimer’s disease. APP has previously been reported to have multiple functions during normal development, and as human and avian APP share 95% homology in amino acid sequence, we have employed a one-trial passive avoidance task in day-old chicks to study its role in the process of memory formation. Administration of anti-APP antibodies raised against human APP, APP-antisense and Aβ during pre-training, prevented memory formation without effects on general behaviour or initial acquisition. Amnesia is apparent by thirty minutes post-training and lasts for at least 24 hr. Injection of APP-derived peptides RERMS (APP328-332) and RER (APP328-330) homologous to the short stretches of amino acids in theKang sequence (APP 319-335), rescue the memory in animals rendered amnestic by previous (anti-APP antibody, antisense and Aβ) pre-treatments. The protected form of RER, with a prolonged half-life (acetylated RER), proved to be effective when injected intracranially and/or peripherally. The tripeptide RER appears to exerts its biological activity by binding to two neuronal plasma membrane proteins (60 and 110kDa). The results obtained in this study suggest that RER alleviates memory deficits via receptor-mediated events, and that short APP-derived peptides might represent a novel group of therapeutically active molecules for the alleviation of memory deficits in age-related dementias.
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