Genetic variation in the 5-HT2A receptor and altered neocortical [H-3] ketanserin binding in Alzheimer's disease
Holmes, C., McCulley, M., Nicoll, J.A.R., Alder, J.T., Chen, C.P.L.H. and Francis, P.T. (2007) Genetic variation in the 5-HT2A receptor and altered neocortical [H-3] ketanserin binding in Alzheimer's disease. Neuroscience Letters, 420, (1), 58-60. (doi:10.1016/j.neulet.2007.04.009).
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A common intronic single nucleotide polymorphism (T102C) in the 5-HT2A receptor gene is associated with the development of different neuropsychiatric symptoms, including hallucinations and depressive symptoms in Alzheimer's disease (AD). Differential 5-HT2A receptor binding has also been associated with the development of these symptoms in AD. However, the relationship between 5-HT2A (T102C) genotype and 5-HT2A receptor binding in AD and control human brains has not been examined. We examined the association between different 5-HT2A (T102C) genotypes and [H-3] ketanserin binding in the temporal and frontal cortex of 20 AD and 14 control human brains. In homozygotes, but not heterozygotes, there was a significant reduction in B-max values for [H-3] ketanserin binding in both areas of cortex in AD compared with control subjects. This study suggests a mechanism for the generation of different neuropsychiatric symptoms in AD from a single nucleotide polymorphism with reduced receptor binding in T102C 5-HT2A receptor gene homozygotes correlating with susceptibility to depressive symptoms, whereas the relative preservation of receptor binding in heterozygotes with AD correlating with susceptibility to hallucinations.
|Keywords:||depression, polymorphism,5-ht2a, ad, neurochemistry, memory, genetics, pathology, receptor-binding, heterosis, human brain, association, brain, alzheimer's disease|
|Subjects:||R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Clinical Neurosciences
University Structure - Pre August 2011 > School of Medicine
University Structure - Pre August 2011 > School of Medicine > Human Genetics
|Date Deposited:||12 Sep 2008|
|Last Modified:||01 Jun 2011 05:09|
|Contributors:||Holmes, C. (Author)
McCulley, M. (Author)
Nicoll, J.A.R. (Author)
Alder, J.T. (Author)
Chen, C.P.L.H. (Author)
Francis, P.T. (Author)
|Date:||8 June 2007|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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