Loss of serotonin 2A receptors exceeds loss of serotonergic projections in early Alzheimer's disease: a combined [C]DASB and [F]altanserin-PET study

In patients with Alzheimer's disease (AD), postmortem and imaging studies have revealed early and prominent reductions in cerebral serotonin 2A (5-HT_2A) receptors. To establish if this was due to a selective disease process of the serotonin system, we investigated the cerebral 5-HT_2A receptor and the serotonin transporter binding, the latter as a measure of serotonergic projections and neurons. Twelve patients with AD (average Mini Mental State Examination MMSE]: 24) and 11 healthy age-matched subjects underwent positron emission tomography (PET) scanning with ¹⁸F]altanserin and ¹¹C]N,N-Dimethyl-2-(2-amino-4-cyanopheylthio)benzylamine (¹¹C]DASB). Overall ¹⁸F]altanserin binding was markedly reduced in AD by 28%-39% (p = 0.02), whereas the reductions in ¹¹C]DASB binding were less prominent and mostly insignificant, except for a marked reduction of 33% in mesial temporal cortex (p = .0005). No change in ¹¹C]DASB binding was found in the midbrain. We conclude that the prominent reduction in neocortical 5-HT_2A receptor binding in early AD is not caused by a primary loss of serotonergic neurons or their projections.