Functional Connectivity Analysis in Heterozygous Glucocerebrosidase Mutation Carriers

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Alterations in striatocortical circuit functional connectivity (FC) may precede clinical symptoms of Parkinson's disease (PD).
• Glucocerebrosidase (GBA) mutations are a significant risk factor for developing PD.

Purpose of the Study:

• To investigate striatocortical FC in asymptomatic carriers of heterozygous GBA mutations.
• To identify potential early network changes associated with PD risk.

Main Methods:

• Included 21 asymptomatic GBA mutation carriers and 18 healthy controls.
• Utilized structural and functional MRI for FC analysis using a seed-based approach.
• Performed GBA mutation analysis and clinical evaluations.

Main Results:

• Asymptomatic GBA mutation carriers showed significant differences in striatocortical FC compared to healthy controls.
• No significant differences in neurological examination or UPDRS Part III scores were observed between groups.
• A statistically significant difference in Mini-Mental State Examination scores was noted between carriers and controls.

Conclusions:

• Striatocortical FC alterations are detectable in asymptomatic individuals carrying GBA mutations.
• These findings suggest potential network changes occurring during the preclinical phase of Parkinson's disease.
• Early detection of network alterations may offer insights into PD pathogenesis.