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[3H]GR113808 binding to serotonin 5-HT4 receptors in the postmortem neocortex of Alzheimer disease: a clinicopathological study


Abnormalities in neural transmission of serotonin (5-HT) may play a role in both cognitive and neuropsychiatric features of Alzheimer disease (AD). We measured 5-HT4 receptors in the postmortem frontal and temporal cortex of 34 AD subjects and 15 controls by radioligand binding with [3H]GR113808. Receptor binding data was then correlated with prospectively assessed cognitive (Mini-Mental State Examination, MMSE) and behavioral (Present Behavioural Examination, PBE) data. [3H]GR113808 binding affinity (KD) and density (Bmax) in AD were unchanged compared to controls in both cortical regions, and did not correlate with MMSE or PBE data. The binding parameters were also not related to disease duration, senile plaque and neurofibrillary tangle counts, and neuroleptic medication. We conclude that unlike other 5-HT receptors, 5-HT4 receptor binding affinity and density do not seem to be affected in the frontal and temporal cortex in AD and may not have a direct role in the clinical features of the disease.

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Received October 10, 2002; accepted February 18, 2003 Published online April 22, 2003

Acknowledgments This work is supported by the National Medical Research Council of Singapore, the Department of Clinical Research, Singapore General Hospital, and the Wellcome Trust. We thank Dr. B. McDonald, Dr. J. Keene, and J. Carter for assistance with the collection and classification of data and postmortem samples.

Authors' address: Dr. C. P. Chen, Neuroscience Research Laboratory, Block 6, Level 6, Room A5, Singapore General Hospital, Outram Road, Singapore 169608, e-mail:

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Lai, M., Tsang, S., Francis, P. et al. [3H]GR113808 binding to serotonin 5-HT4 receptors in the postmortem neocortex of Alzheimer disease: a clinicopathological study. J Neural Transm 110, 779–788 (2003).

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  • Keywords: Alzheimer disease
  • serotonin 5-HT4 receptors
  • neuropsychiatric symptoms
  • cognitive decline
  • postmortem brains
  • frontal cortex
  • temporal cortex.