LRRK2 and GBA1 variant carriers have higher urinary bis(monacylglycerol) phosphate concentrations in PPMI cohorts

Kalpana M. Merchant; Tanya Simuni; Janel Fedler; Chelsea Caspell-Garcia; Michael Brumm; Kelly Nh Nudelman; Elizabeth Tengstrandt; Frank Hsieh; Roy N. Alcalay; Christopher Coffey; Lana Chahine; Tatiana Foroud; Andrew Singleton; Daniel Weintraub; Samantha Hutten; Todd Sherer; Brit Mollenhauer; Andrew Siderowf; Caroline Tanner; Ken Marek; Parkinson’s Progression Markers Initiative

doi:10.1038/s41531-023-00468-2

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LRRK2 and GBA1 variant carriers have higher urinary bis(monacylglycerol) phosphate concentrations in PPMI cohorts

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LRRK2 and GBA1 variant carriers have higher urinary bis(monacylglycerol) phosphate concentrations in PPMI cohorts

Kalpana M. Merchant, Tanya Simuni, Janel Fedler, Chelsea Caspell-Garcia, Michael Brumm, Kelly Nh Nudelman, Elizabeth Tengstrandt, Frank Hsieh, Roy N. Alcalay, Christopher Coffey, …

NPJ Parkinson's disease, Vol.9, 30

02/01/2023

DOI: 10.1038/s41531-023-00468-2

PMCID: PMC9974978

PMID: 36854767

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Abstract

We quantified concentrations of three isoforms of the endolysosomal lipid, bis(monoacylglycerol) phosphate (BMP) in the 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). The 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 3-7× 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.

Brain Disorders

Neurological

Neurosciences

Neurodegenerative

the Parkinson’s Progression Markers Initiative

2.1 Biological and endogenous factors

Parkinson's Disease

Aetiology

Details

Title: Subtitle: LRRK2 and GBA1 variant carriers have higher urinary bis(monacylglycerol) phosphate concentrations in PPMI cohorts
Creators: Kalpana M. Merchant
Tanya Simuni - University of Iowa
Janel Fedler - University of Iowa
Chelsea Caspell-Garcia - University of Iowa
Michael Brumm - University of Iowa
Kelly Nh Nudelman
Elizabeth Tengstrandt
Frank Hsieh
Roy N. Alcalay
Christopher Coffey - University of Iowa
Lana Chahine
Tatiana Foroud
Andrew Singleton
Daniel Weintraub
Samantha Hutten
Todd Sherer
Brit Mollenhauer
Andrew Siderowf
Caroline Tanner
Ken Marek
Parkinson’s Progression Markers Initiative
Resource Type: Journal article
Publication Details: NPJ Parkinson's disease, Vol.9, 30
DOI: 10.1038/s41531-023-00468-2
PMID: 36854767
PMCID: PMC9974978
NLM abbreviation: NPJ Parkinsons Dis
ISSN: 2373-8057
Publisher: Nature Publishing Group
Language: English
Date published: 02/01/2023
Academic Unit: Biostatistics
Record Identifier: 9984530385802771

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