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Comparative Study
. 2005 May;179(3):673-7.
doi: 10.1007/s00213-004-2077-2. Epub 2004 Nov 18.

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

M K Lai  1 , S W Tsang, J T Alder, J Keene, T Hope, M M Esiri, P T Francis, C P Chen
Affiliations
Comparative Study

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

M K Lai et al. Psychopharmacology (Berl). 2005 May.

Abstract

Rationale: Previous studies have demonstrated reductions of serotonin 5-HT 2A 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-HT 2A receptor alterations with cognitive decline in AD.

Methods: Postmortem frontal and temporal cortical 5-HT 2A 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-HT 2A 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-HT 2A 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-HT 2A 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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