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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), pp. 555-561. (doi:10.1016/j.nbd.2005.12.016).

Record type: Article


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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Published date: June 2006
Keywords: apolipoprotein-e genotype, nicotinic receptor, ad, senile dementia, dementia, choline acetyltransferase, acetyltransferase activity, rat-brain, transgenic mice, disease, e4 allele, muscarinic receptors


Local EPrints ID: 62474
ISSN: 0969-9961
PURE UUID: 34b32106-c7bf-4afa-a172-4f83a78af645
ORCID for James A.R. Nicoll: ORCID iD

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Date deposited: 12 Sep 2008
Last modified: 17 Jul 2017 14:20

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Author: Mitchell K.P. Lai
Author: Shirley W.Y. Tsang
Author: Monica Garcia-Alloza
Author: Stephen L. Minger
Author: Margaret M. Esiri
Author: Peter T.H. Wong
Author: Christopher P.L.H. Chen
Author: María J. Ramirez
Author: Paul T. Francis

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