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).
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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.
|Keywords:||apolipoprotein-e genotype, nicotinic receptor, ad, senile dementia, dementia, choline acetyltransferase, acetyltransferase activity, rat-brain, transgenic mice, disease, e4 allele, muscarinic receptors|
|Subjects:||R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
R Medicine > RS Pharmacy and materia medica
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Developmental Origins of Health and Disease
University Structure - Pre August 2011 > School of Medicine > Clinical Neurosciences
University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair
|Date Deposited:||12 Sep 2008|
|Last Modified:||27 Mar 2014 18:44|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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