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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- Lai, M.K., Tsang, S.W., Alder, J.T. et al. Psychopharmacology (2005) 179: 673. doi:10.1007/s00213-004-2077-2
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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.
To correlate neocortical 5-HT2A receptor alterations with cognitive decline in AD.
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.
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.
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.