Noradrenergic alterations in Parkinson’s disease: a combined 11C-yohimbine PET/neuromelanin MRI study

Abstract

Abstract Degeneration of the noradrenergic system is now considered a pathological hallmark of Parkinson’s disease but little is known about its consequences in terms of parkinsonian manifestations. Here, we evaluate two aspects of the noradrenergic system using multimodal in vivo imaging in patients with Parkinson’s disease and healthy controls: the pigmented cell bodies of the locus coeruleus with neuromelanin sensitive MRI and the density of α2-adrenergic receptors (ARs) with PET using [11C]yohimbine. Thirty patients with Parkinson’s disease and thirty age- and sex-matched healthy control subjects were included. Patient’s symptoms characteristics were assessed using the MDS-UPDRS scale. Patients showed reduced neuromelanin signal intensity in the locus coeruleus compared to controls, and diminished [11C]yohimbine binding in widespread cortical regions including the motor cortex as well as in the insula, the thalamus and the putamen. Clinically, locus coeruleus neuronal loss was correlated with motor (bradykinesia, motor fluctuations, tremor) and non-motor (fatigue, apathy, constipation) symptoms. A reduction of α2-ARs availability in the thalamus was associated with tremor, while a reduction in the putamen, the insula and the superior temporal gyrus was associated with anxiety. These findings highlight a multifaceted alteration of the noradrenergic system in Parkinson’s disease since locus coeruleus and α2-ARs degenerations were found to be partly uncoupled. These findings raise important issues about noradrenergic dysfunctions that may encourage the search for new drugs targeting this system, including α2-ARs, for the treatment of Parkinson’s disease.