Association of Serum Vitamin B12 with LRRK2 Urinary Exosomal Markers in Early Parkinson’s Disease
Chadwick Christine1, Peggy Auinger2, Esther Forti3, Lyvin Tat3, Noemi Cannizzaro3, Ralph Green3, Michael Schwarzschild4, Andrew West5
1University of California San Francisco, 2Center for Health and Technology and Department of Neurology, University of Rochester, 3University of California Davis Medical Center, 4Massachusetts General Hospital, 5Duke University
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.
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