Association of Serum Vitamin B12 with LRRK2 Urinary Exosomal Markers in Early Parkinson's Disease (P3-5.022).

OBJECTIVE: To test for associations of serum vitamin B12 with urinary exosomal markers of Leucine-Rich Repeat Kinase 2 (LRRK2) in patients with early Parkinson's disease (PD). BACKGROUND: LRRK2 is an enzyme for which certain mutations are associated with increased kinase activity and dominantly inherited PD. Urinary exosomal measurements of LRRK2 activity have been shown to mirror brain LRRK2 activity levels and for Rab phosphorylation to increase over time in PD patients. Since preclinical research has shown that vitamin B12 allosterically inhibits LRRK2 and reduces α-synuclein fibrillogenesis, we sought to determine whether serum B12 levels were associated with urinary LRRK2 exosomal markers in SURE-PD, a 2-year randomized trial of inosine for participants with early PD. DESIGN/METHODS: Baseline and end of study urine and serum samples from the SURE-PD study were obtained. Measurements of LRRK2, pRab and total Rab in urinary extracellular vesicles were obtained using immunoblotting technique. Vitamin B12 was measured using Abbott Alinity Chemiluminescent Microparticle Immunoassay. RESULTS: Paired measurements of serum B12 and LRRK2 urinary exosomal markers were available in a subset of 50 participants (30 female and 20 male) at baseline and 54 (33 female and 21 male) at end of study. No relationship between B12 and total LRRK2 levels was observed. In females, the ratio of pRab/total Rab was inversely correlated with B12 (r=-0.4, p=0.03, n=31 with pRab > lower limit of quantification (LLOQ)) at the end of study and (r=-0.23, p=0.47, n=12 > LLOQ) at baseline. No significant correlations were seen in males. CONCLUSIONS: A possible inverse correlation was observed at the end of study between the pRab/total Rab ratio and B12 in females, but not in males. The reasons for this apparent association may reflect time and sex differences or the lower sample size. Further study of this relationship in a larger cohort is warranted. Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff. Disclosure: The institution of Dr. Christine has received research support from Neurocrine Biosciences. The institution of Dr. Christine has received research support from Brain Neurotherapy Bio, Inc. The institution of Dr. Christine has received research support from Michael J Fox Foundation for Parkinson's Research. The institution of Dr. Christine has received research support from Annovis Bio. The institution of Dr. Christine has received research support from Aspen Neurosciences. Ms. Auinger has nothing to disclose. The institution of Esther Rodriguez-Forti has received research support from The Michael J. Fox Foundation for Parkinson's Research, Grant 18462 and NIH R01NS110879. Lyvin Tat has nothing to disclose. Author has nothing to discloseAuthor has nothing to discloseThe institution of Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bial Biotech (indirectly, as a service of the Parkinson Study Group service). The institution of Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen (indirectly, as a service of the Parkinson Study Group service). The institution of Dr. Schwarzschild has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB (indirectly, as a service of the Parkinson Study Group service). Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. The institution of Dr. Schwarzschild has received research support from NIH. The institution of Dr. Schwarzschild has received research support from Parkinson's Foundation. The institution of Dr. Schwarzschild has received research support from Michael J Fox Foundation. The institution of Dr. Schwarzschild has received research support from Farmer Family Foundation. Dr. Schwarzschild has a non-compensated relationship as a Chair, Executive Committee with the Parkinson Study Group that is relevant to AAN interests or activities. Prof. West has nothing to disclose.

Duke Scholars

Author Andrew Bradley West Pharmacology & Cancer Biology