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

Abstract

Rationale: Previous studies have demonstrated reductions of serotonin 5-HT 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 receptor alterations with cognitive decline in AD. Methods: Postmortem frontal and temporal cortical 5-HT receptors were measured by [ H]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 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 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 receptors may predict for faster cognitive decline in AD, and point to serotomimetics as potentially useful adjuvants to cholinergic replacement therapies. © Springer-Verlag 2004.