Nigrostriatal upregulation of 5-HT2A receptors correlates with motor dysfunction in progressive supranuclear palsy.

A dysfunction of multiple neurotransmitter systems is assumed as a neurochemical basis of the akinetic-rigid syndrome of progressive supranuclear palsy (PSP). In vitro studies have produced conflicting results on the serotoninergic system in PSP. We, therefore, studied the binding potential of the serotonin 2A (5-HT(2A)) receptor ligand [18F]altanserin in 8 patients with clinically probable PSP and 13 healthy controls using positron emission tomography. We found an up-regulation of 5-HT(2A) receptors in the substantia nigra and, to a lower degree, in the striatum, while neocortical 5- HT(2A) receptor densities showed no changes upon partial-volume correction. Nigral and striatal receptor changes were significantly correlated with patients' scores of motor dysfunction (UPDRS III, PSP-rating scale) pointing to a functional relevance of the described findings.