Abstract Details

Title Genotype-specific white matter microstructural alterations in prodromal Parkinson’s disease

Topic Movement Disorders

Presentation(s) P6 - Poster Session 6 (5:30 PM-6:30 PM)

Poster/Presentation
Number 5-002

Background Diffusion tensor imaging (DTI) studies have demonstrated WM changes in PD patients, as well as in healthy LRRK2 NMCs believed to be at increased risk for PD. To date, WM microstructural fingerprints of GBA mutation carriers remains unclear.

Objective

We investigated genotype-related white matter (WM) changes in GBA and LRRK2 non-manifesting mutation carriers (NMCs), and explored the relationship between WM integrity and the MDS likelihood-ratio (LR) scores for prodromal Parkinson's disease (PD).

Design/Methods

First-degree relatives of PD patients (> 40 years) underwent genetic phenotyping, MRI scans acquiring DTI datasets, and clinical assessments. Tract-based spatial statistics (TBSS) was performed based on DTI datasets. WM differences between the different genotype groups were investigated. LR scores were calculated for all participants, with participants re-grouped based on LR scores (LR+: ≥65 vs. LR- < 65). P < 0.05 FDR-corrected for multiple comparisons was adopted for all comparisons.

Results

Genetic phenotyping resulted in: N= 34 non-manifesting non-carriers (NMNC) (53.55±10.51 yrs), N=26 GBA NMC (52.85 ± 8.81 yrs), and N= 25 LRRK2 NMC (50.52±7.56 yrs). GBA NMCs showed higher fractional anisotropy (FA) in the posterior cerebellar lobule (VI) and the right inferior fronto-occipital fasciculus, and lower FA in the left corona radiata compared to NMNC group. LRRK2 NMCs demonstrated higher FA in the corpus-callosum and bilateral anterior corona-radiata, and lower FA in the midbrain compared to NMNCs. Compared to LRRK2 NMCs, GBA NMCs showed higher FA in midbrain and lower FA in the left corona radiata. Finally, higher FA the corpus-callosum and thalamic radiation in LR- compared to LR+ group was detected. The latter showed higher FA values in the left retrolenticular part of internal capsule and the right superior corona radiata compared to LR-.

Conclusions WM microstructural changes can be observed in individuals at high risk for PD prior to disease symptoms onset.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Nir Giladi, MD, FAAN (Tel-Aviv Medical Center)	Dr. Giladi has received personal compensation in the range of $0-$499 for serving as a Consultant for Sionara. Dr. Giladi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NeuroDerm. Dr. Giladi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pharma2B. Dr. Giladi has stock in Vibrant. Dr. Giladi has stock in Lysosomal Therapeutics . The institution of Dr. Giladi has received research support from The Michael J Fox Foundation. The institution of Dr. Giladi has received research support from The National Parkinson Foundation. The institution of Dr. Giladi has received research support from The European Union . The institution of Dr. Giladi has received research support from The Israel Science Foundation. The institution of Dr. Giladi has received research support from Biogen . The institution of Dr. Giladi has received research support from Ionis. The institution of Dr. Giladi has received research support from Sieratzki Family Foundation . The institution of Dr. Giladi has received research support from The Aufzien Academic Center in Tel-Aviv University.
Anat Mirelman	Anat Mirelman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie . Anat Mirelman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bial. The institution of Anat Mirelman has received research support from Department of Defense. The institution of Anat Mirelman has received research support from MJFF. The institution of Anat Mirelman has received research support from JPND. The institution of Anat Mirelman has received research support from EU-Horizon 2020.
Avner Thaler, MD (Tel-Aviv Souraski Medical Center)	The institution of Dr. Thaler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ABBVIE. The institution of Dr. Thaler has received research support from MJFF.