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).

Abstract

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.

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Contributors

Author: C. Holmes

Author: J.A.R. Nicoll

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