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

Journal article

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.

Authors: Lai, M; Tsang, S; Alder, J; Keene, J; Hope, T

• Publication status: Published
• Journal: Psychopharmacology
• Volume: 179
• Issue: 3
• Pages: 673-677
• Publication date: 2005-05-01
• DOI: 10.1007/s00213-004-2077-2
• EISSN: 1432-2072
• ISSN: 0033-3158
• Language: English
• Keywords: Longitudinal Studies; Humans; Temporal Lobe; Aged; Alzheimer Disease; Cognition Disorders; Female; Male; Aged, 80 and over; Receptor, Serotonin, 5-HT2A; Protein Binding