LRRK2 and GBA1 variant carriers have higher urinary bis(monacylglycerol) phosphate concentrations in PPMI cohorts
Year: 2023
Type: article
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.
Source: npj Parkinson s Disease
Authors: Kalpana M. Merchant, Tanya Simuni, Janel Fedler, Chelsea Caspell-Garcia, Michael Brumm, Kelly N. H. 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, the Parkinson’s Progression Markers Initiative
Institutions: Northwestern University, University of Iowa, Indiana University School of Medicine, Columbia University, University of Pittsburgh, Indiana University Indianapolis, National Institutes of Health, National Institute on Aging, University of Pennsylvania, Michael J. Fox Foundation, Universitätsmedizin Göttingen, University of California, San Francisco, Institute for Neurodegenerative Disorders
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,290
Funders: U.S. Department of Defense, U.S. Department of Veterans Affairs, Michael J. Fox Foundation for Parkinson's Research, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Sanofi, Biogen, Teva Pharmaceutical Industries, Indiana State Department of Health, San Diego State University, University of Texas at Austin, Sunovion, National Collegiate Athletic Association, Parkinson's Foundation, US WorldMeds, Neurocrine Biosciences, Prothena, Voyager Therapeutics, Bundesministerium für Bildung und Forschung, Stifterverband, Sun Pharma, Deutsche Parkinson Vereinigung, National Institutes of Health, Genentech, Allergan, National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke
OpenAlex ID: W4322719649