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We quantified concentrations of three isoforms of the endolysosomal lipid, bis(monoacylglycerol) phosphate (BMP) in urine of deeply phenotyped cohorts in the Parkinson’s Progression Markers Initiative: LRRK2 G2019S PD (N = 134) and non-manifesting carriers (NMC) (G2019S + NMC; N = 182), LRRK2 R1441G PD (N = 15) and R1441G + NMC (N = 15), GBA1 N409S PD (N = 76) and N409S + NMC (N = 178), sporadic PD (sPD, N = 379) and healthy controls (HC) (N = 190). Effects of each mutation and disease status were analyzed using nonparametric methods. Longitudinal changes in BMP levels were analyzed using linear mixed models. At baseline, all LRRK2 carriers had 3-7x higher BMP levels compared to HC, irrespective of the disease status. GBA1 N409S carriers also showed significant, albeit smaller, elevation (~ 30–40%) in BMP levels compared to HC. In LRRK2 G2019S PD, urinary BMP levels remained stable over two years. Furthermore, baseline BMP levels did not predict disease progression as measured by striatal DaT imaging, MDS-UPDRS III Off or MoCA in any of the cohorts. These data support the utility of BMP as a target modulation biomarker in therapeutic trials of genetic and sPD but not as a prognostic or disease progression biomarker.

Urine Bis(monoacylglcerol) phosphate (BMP) has been identified as a biomarker that identifies carriers variants in the LRRK2 gene. The purpose of this study was to investigate BMP in patients with LRRK2-associated Parkinson’s disease in a longitudinal study. We found that BMP was elevated in patients with LRRK2 PD compared to sporadic PD. We did not identify phenotypic variation associated with LRRK2.

Background: We examined 2-year longitudinal change in clinical features and biomarkers in LRRK2 non-manifesting carriers (NMCs) versus healthy controls (HCs) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). Methods: We analyzed 2-year longitudinal data from 176 LRRK2 G2019S NMCs and 185 HCs. All participants were assessed annually with comprehensive motor and non-motor scales, dopamine transporter (DAT) imaging and biofluid biomarkers. The latter included cerebrospinal fluid (CSF) Abeta, total tau and phospho-tau; serum urate and neurofilament light chain (NfL); and urine bis(monoacylglycerol) phosphate (BMP). Findings: At baseline, LRRK2 G2019S NMCs had a mean (SD) age of 62 (7.7) years and were 56% female. 13% had DAT deficit (defined as LRRK2 NMCs developed PD during the follow up. Interpretation: We observed no significant longitudinal change in clinical or biomarker measures in LRRK2 G2019S NMCs in this large, well-characterized cohort. Longer follow up and further selection of NMCs at highest risk for conversion is required for future prevention clinical trials.