Dataset Information

Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson's disease.

ABSTRACT: Elevated urine bis(monoacylglycerol)phosphate (BMP) levels have been found in gain-of-kinase function LRRK2 G2019S mutation carriers. Here, we have expanded urine BMP analysis to other Parkinson's disease (PD) associated mutations and found them to be consistently elevated in carriers of LRRK2 G2019S and R1441G/C as well as VPS35 D620N mutations. Urine BMP levels are promising biomarkers for patient stratification and potentially target engagement in clinical trials of emerging targeted PD therapies.

SUBMITTER: Gomes S

PROVIDER: S-EPMC10073226 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson's disease.

Gomes Sara S Garrido Alicia A Tonelli Francesca F Obiang Donina D Tolosa Eduardo E Martí Maria José MJ Ruiz-Martínez Javier J Vinagre-Aragón Ana A Hernandez-Eguiazu Haizea H Croitoru Ioana I Marshall Vicky L VL Koenig Theresa T Hotzy Christoph C Hsieh Frank F Sakalosh Marianna M Tengstrand Elizabeth E Padmanabhan Shalini S Merchant Kalpana K Bruecke Christof C Pirker Walter W Zimprich Alexander A Sammler Esther E

NPJ Parkinson's disease 20230404 1

Elevated urine bis(monoacylglycerol)phosphate (BMP) levels have been found in gain-of-kinase function LRRK2 G2019S mutation carriers. Here, we have expanded urine BMP analysis to other Parkinson's disease (PD) associated mutations and found them to be consistently elevated in carriers of LRRK2 G2019S and R1441G/C as well as VPS35 D620N mutations. Urine BMP levels are promising biomarkers for patient stratification and potentially target engagement in clinical trials of emerging targeted PD thera ...[more]

PMID: 37015928

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Project description:BackgroundLRRK2 mutations are a common cause of dominantly inherited PD. Previous studies showed decreases in urine levels of didocohexaenoyl (22:6) bis(monoacylglycerol)phosphate in LRRK2-knockout mice and in non-human primates treated with LRRK2 kinase inhibitors. We hypothesized that urine levels of bis(monoacylglycerol)phosphate isoforms will be higher in individuals with a PD-causing gain-of-kinase function mutation, LRRK2 G2019S. The objective of this study was to investigate alterations in urinary phospholipids as biomarkers of LRRK2 mutations and Parkinson's disease status/phenotypes.MethodsUltra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to assess 54 bioactive phospholipids in urine from the LRRK2 Cohort Consortium (n = 80). To confirm and extend the findings, urine from an independent LRRK2 cohort from Columbia University Irving Medical Center (n = 116) was used. Both cohorts were composed of LRRK2 G2019S carriers and non-carriers with and without PD.ResultsIn each cohort, 4 bis(monoacylglycerol)phosphate isoforms (di-18:1-bis[monoacylglycerol]phosphate, didocohexaenoyl [22:6] bis[monoacylglycerol] phosphate, 2,2'-di-22:6-bis[monoacylglycerol]phosphate, and 2,2'-di-18:1-bis[monoacylglycerol]phosphate) were significantly higher (2.5- to 4.3-fold) in G2019S carriers compared with non-carriers. Interestingly, 2,2'-di-18:1-bis(monoacylglycerol)phosphate levels were marginally higher in LRRK2 carriers with PD than in those without PD (P = 0.045). Moreover, increased 2,2' and total di-22:6-bis(monoacylglycerol)phosphate were associated with worse cognitive status assessed by the Montreal Cognitive Assessment (P = 0.0033 and 0.0144, respectively).ConclusionsThe observed association of bis(monoacylglycerol)phosphate isoforms with LRRK2 G2019S mutation, PD status among G2019S carriers, and correlation with cognitive decline suggest the potential use of urinary bis(monoacylglycerol)phosphate isoforms as biomarkers for clinical trials of LRRK2-targeted therapies. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Dataset Information

Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson's disease.

Publications

Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson's disease.

Similar Datasets

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