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

Lai, Mitchell K.P., Tsang, Shirley W.Y., Garcia-Alloza, Monica, Minger, Stephen L., Nicoll, James A.R., Esiri, Margaret M., Wong, Peter T.H., Chen, Christopher P.L.H., Ramirez, María J. and Francis, Paul T. (2006) Selective effects of the APOE epsilon 4 allele on presynaptic cholinergic markers in the neocortex of Alzheimer's disease. Neurobiology of Disease, 22 (3), 555-561. (doi:10.1016/j.nbd.2005.12.016).

Abstract

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.

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Contributors

Author: James A.R. Nicoll

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