Acetylcholine-Dopamine Interactions in Neurodegenerative Diseases: a Molecular Imaging Approach

The question of how acetylcholine (ACh) and dopamine (DA) could be involved together in the pathophysiology of some neurodegenerative disorders is essential, particularly in dementia with Lewy bodies (DLB). The present study aims at assessing an in vivo molecular imaging method of both ACh and DA brain systems using single photon emission computed tomography. In the first part of the present study, a method based on pharmacokinetic analysis making it possible to quantify ACh neurons in vivo, using [¹²³I]-IBVM, a specific radioligand of vesicular acetylcholine transporter, was developed and validated in healthy subjects and Alzheimer's disease patients. Then, we showed the ability of our method to demonstrate a differential alteration of ACh pathways in Progressive Supranuclear Palsy and Multiple System Atrophy patients. In the last part of this study, we imaged for the first time both ACh and DA systems in DLB patients, using not only [¹²³I]-IBVM, but also [¹²³I]-FP-CIT, a specific radioligand of dopamine transporter. Concomitantly, a behavioral exploration of hallucinations, fluctuating cognition and disturbances of circadian rhythms was achieved in these patients, as well as a neuropsychological examination. This study is currently in progress. The first results show consistent links between imaging and clinical data. (author)