Imaging in Glucocerebrosidase-Associated Parkinsonism: Current Status and Implications for Pathophysiology

Abstract

Background: Glucocerebrosidase (GBA) mutations have been described as the most prevalent in Parkinson's disease (PD) and in Lewy body dementia, accounting for up to 7 and 13.8% of cases, respectively. To elucidate the pathophysiology of idiopathic Parkinson's disease (iPD), the pathogenic mechanisms leading to Lewy body accumulation in GBA-associated parkinsonism (GBA-PD) are a matter of current research. However, only few imaging studies, conducted on small GBA-PD patient cohorts, exist.

Methods: We provide an overview of current structural and functional imaging studies in patients with Gaucher's disease and parkinsonism and in GBA-PD patients, underlining the main differences compared to iPD.

Results: A limited number of PET studies have been conducted in GBA-PD, exploring brain metabolism and dopaminergic presynaptic and postsynaptic function. Moreover, structural MRI and spectroscopy studies recently evidenced the differences with iPD, aiding to understand of some peculiar aspects of iPD. Finally, new evidence from transcranial sonography confirms the technique's role in the study of GBA-PD and highlights the additional involvement of the raphe nucleus.

Conclusions: Further imaging studies conducted in a broader population of early GBA-PD are warranted to characterize the disease and elucidate the pathophysiological mechanisms underlying GBA-PD and to understand GBA implications in iPD.