Objective: This study aimed to compare the alterations in the cortico-striatal functional connectivity (FC) of drug-naïve Parkinson’s disease (PD) patients with the leucine-rich repeat kinase 2 (LRRK2) mutation in the ethnic Han-Chinese PD population using voxel-based analysis of neuroimaging data.

Background: LRRK2 has been recently identified as a causative gene of PD, with the most common mutations of R1628P and G2385R in the ethnic Han-Chinese PD population. However, the pathogenic mechanism of the LRRK2 mutation remains largely unknown.

Methods: Resting-state fMRI was used to assess FC focusing on striatal subregions of 11 PD patients with the LRRK2 mutation, 11 PD patients without such mutation, and 22 healthy control subjects in the ethnic Han-Chinese PD population.

Results: When compared with the healthy control subjects, both subgroups of PD patients showed alterations in FC within sensorimotor-striatal and posterior putamen-striatal circuits. However, relative to the subgroup of patients without the LRRK2 mutation, the subgroup of patients with the LRRK2 mutation exhibited decreased FC between putamen and bilateral superior frontal gyri, precuneus and calcarine gyri. Furthermore, the FC between putamen and bilateral superior frontal gyri decreased with age in LRRK2 mutation carriers but not in noncarriers.

Conclusions: The differences of FC between PD patients with and without the LRRK2 mutation may support the further research of the distinct pathological mechanism resulting from the LRRK2 mutation in the ethnic Han-Chinese PD population. Our result is preliminary and further investigations are needed.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/altered-intrinsic-brain-functional-connectivity-in-drug-naive-parkinsons-disease-with-lrrk2-mutation/