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Loss of serotonin 5-HT2A receptors in the postmortem temporal cortex correlates with rate of cognitive decline in Alzheimer’s disease

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Abstract

Rationale

Previous studies have demonstrated reductions of serotonin 5-HT2A receptors in the neocortex of Alzheimer’s disease (AD) patients. However, it is unclear whether such losses play a role in the cognitive decline of AD.

Objectives

To correlate neocortical 5-HT2A receptor alterations with cognitive decline in AD.

Methods

Postmortem frontal and temporal cortical 5-HT2A receptors were measured by [3H]ketanserin binding in aged controls as well as in a cohort of AD patients who had been longitudinally assessed for cognitive decline and behavioral symptoms.

Results

5-HT2A receptor densities in both regions were reduced in severely demented AD patients compared to age-matched controls. In the temporal cortex, this reduction also correlated with the rate of decline of Mini-Mental State Examination (MMSE) scores. The association between 5-HT2A receptor loss and cognitive decline was independent of the effects of choline acetyltransferase (ChAT) activity and presence of behavioral symptoms.

Conclusions

Our data suggest that loss of neocortical 5-HT2A receptors may predict for faster cognitive decline in AD, and point to serotomimetics as potentially useful adjuvants to cholinergic replacement therapies.

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Acknowledgements

This study was supported by the Wellcome Trust, the Medical Research Council of the UK, the Department of Clinical Research, Singapore General Hospital, and the National Medical Research Council of Singapore.

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Authors and Affiliations

  1. Dementia Research Laboratory, Department of Clinical Research, Singapore General Hospital, Outram Road, 169608, Singapore

    M. K. Lai

  2. Neurodegeneration and Clinical Trials Group, The Wolfson Centre for Age-Related Diseases, GKT School of Biomedical Sciences, King’s College London, SE1 1UL, London, UK

    M. K. Lai, J. T. Alder & P. T. Francis

  3. Neurodegenerative Diseases Program, National Neuroscience Institute, Singapore General Hospital, Outram Road, 169608, Singapore

    S. W. Tsang & C. P. Chen

  4. Department of Psychiatry, Warneford Hospital, University of Oxford, OX3 7JX, Oxford, UK

    J. Keene & T. Hope

  5. Department of Clinical Neurology and Neuropathology, Radcliffe Infirmary, University of Oxford, OX2 6HE, Oxford, UK

    M. M. Esiri

Authors
  1. M. K. Lai
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  2. S. W. Tsang
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  3. J. T. Alder
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  4. J. Keene
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  5. T. Hope
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  6. M. M. Esiri
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  7. P. T. Francis
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  8. C. P. Chen
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Corresponding author

Correspondence to C. P. Chen.

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Lai, M.K., Tsang, S.W., Alder, J.T. et al. Loss of serotonin 5-HT2A receptors in the postmortem temporal cortex correlates with rate of cognitive decline in Alzheimer’s disease. Psychopharmacology 179, 673–677 (2005). https://doi.org/10.1007/s00213-004-2077-2

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  • DOI: https://doi.org/10.1007/s00213-004-2077-2

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