Hemisynaptic distribution patterns of presenilins and beta-APP isoforms inthe rodent cerebellum and hippocampus

Healthy brain neurons co-express Alzheimer's disease (AD) related proteins presenilins (PS) and beta-amyloid precursor protein (beta-APP), Deposition of beta-amyloid and PS in the senile plaques of AD brain and their ability to interact in vitro suggest that AD pathology could arise from a defect in the physiological interactions between beta-APP and PS within and/or betwe en neurons. The present study compares the immunocytochemical distribution of PS (1 and 2) and beta-APP major isoforms (695 and 751/770) in the synaps es of the cerebellum and hippocampus of the adult rat and mouse. In the cer ebellar cortex of both species, the four molecules are immunodetected in th e presynaptic or the postsynaptic compartments of synapses, suggesting that they are involved in interneuronal relationships. In contrast, PS and beta -APP are postsynaptic in almost all the immunoreactive synapses of the hipp ocampus. The different distribution patterns of these proteins in cerebella r and hippocampal synapses may reflect specific physiological differences, responsible for differential vulnerability of neurons to AD synaptic pathol ogy. Defective interactions between beta-APP and PS at the synapses could i mpede the synaptic functions of beta-APP, inducing the selective loss of sy napses that accounts for cognitive impairment in AD. (C) 2000 Wiley-Liss, I nc.