Psychopharmacology

, Volume 179, Issue 3, pp 673–677

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

  • M. K. Lai
  • S. W. Tsang
  • J. T. Alder
  • J. Keene
  • T. Hope
  • M. M. Esiri
  • P. T. Francis
  • C. P. Chen
Original Investigation

DOI: 10.1007/s00213-004-2077-2

Cite this article as:
Lai, M.K., Tsang, S.W., Alder, J.T. et al. Psychopharmacology (2005) 179: 673. doi:10.1007/s00213-004-2077-2

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.

Keywords

Alzheimer’s disease Serotonin receptors Neocortex Cognition 

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • M. K. Lai
    • 1
    • 2
  • S. W. Tsang
    • 3
  • J. T. Alder
    • 2
  • J. Keene
    • 4
  • T. Hope
    • 4
  • M. M. Esiri
    • 5
  • P. T. Francis
    • 2
  • C. P. Chen
    • 3
  1. 1.Dementia Research Laboratory, Department of Clinical ResearchSingapore General HospitalSingapore
  2. 2.Neurodegeneration and Clinical Trials Group, The Wolfson Centre for Age-Related DiseasesGKT School of Biomedical Sciences, King’s College LondonLondonUK
  3. 3.Neurodegenerative Diseases Program, National Neuroscience InstituteSingapore General HospitalSingapore
  4. 4.Department of Psychiatry, Warneford HospitalUniversity of OxfordOxfordUK
  5. 5.Department of Clinical Neurology and Neuropathology, Radcliffe InfirmaryUniversity of OxfordOxfordUK

Personalised recommendations