Selective effects of the APOE epsilon 4 allele on presynaptic cholinergic markers in the neocortex of Alzheimer's disease

The effects of the APOE epsilon 4 allele on a range of pre- and postsynaptic cholinergic markers were studied in a cohort of community-based Alzheimer's disease (AD) patients. Compared with age-matched controls, the postmortem AD neocortex showed decreased choline acetyltransferase (ChAT) and acetyl cholinesterase activities, lower muscarinic M2. and nicotinic alpha A beta 2 receptor densities, as well as reduced M1 receptor coupling to G-proteins. However, the A allele was dose-dependently correlated only with higher losses of ChAT activities. AD patients with two epsilon 4 alleles also had more beta-amyloid containing senile plaques in the temporal cortex compared to patients with 0/1 epsilon 4. This study suggests that APOE epsilon 4 selectively affects presynaptic cholinergic function which may contribute to the clinical and neuropathological features of AD