title: Elevated GM3 plasma concentration in idiopathic Parkinson's disease: A lipidomic analysis.
abstract: Parkinson's disease (PD) is a common neurodegenerative disease whose pathological hallmark is the accumulation of intracellular α-synuclein aggregates in Lewy bodies. Lipid metabolism dysregulation may play a significant role in PD pathogenesis; however, large plasma lipidomic studies in PD are lacking. In the current study, we analyzed the lipidomic profile of plasma obtained from 150 idiopathic PD patients and 100 controls, taken from the 'Spot' study at Columbia University Medical Center in New York. Our mass spectrometry based analytical panel consisted of 520 lipid species from 39 lipid subclasses including all major classes of glycerophospholipids, sphingolipids, glycerolipids and sterols. Each lipid species was analyzed using a logistic regression model. The plasma concentrations of two lipid subclasses, triglycerides and monosialodihexosylganglioside (GM3), were different between PD and control participants. GM3 ganglioside concentration had the most significant difference between PD and controls (1.531±0.037 pmol/μl versus 1.337±0.040 pmol/μl respectively; p-value = 5.96E-04; q-value = 0.048; when normalized to total lipid: p-value = 2.890E-05; q-value = 2.933E-03). Next, we used a collection of 20 GM3 and glucosylceramide (GlcCer) species concentrations normalized to total lipid to perform a ROC curve analysis, and found that these lipids compare favorably with biomarkers reported in previous studies (AUC = 0.742 for males, AUC = 0.644 for females). Our results suggest that higher plasma GM3 levels are associated with PD. GM3 lies in the same glycosphingolipid metabolic pathway as GlcCer, a substrate of the enzyme glucocerebrosidase, which has been associated with PD. These findings are consistent with previous reports implicating lower glucocerebrosidase activity with PD risk.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, United States of America.|Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Robin B
authors.initials: RB
authors.lastname: Chan
authors.affiliation: Department of Biomedical Informatics, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Adler J
authors.initials: AJ
authors.lastname: Perotte
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Bowen
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Liong
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Shorr
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, United States of America.|Department of Neurology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Marder
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Un J
authors.initials: UJ
authors.lastname: Kang
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Waters
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Oren A
authors.initials: OA
authors.lastname: Levy
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, United States of America.|Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Yimeng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Biomedical Informatics, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Hong Bin
authors.initials: HB
authors.lastname: Shim
authors.affiliation: Department of Biomedical Informatics, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Itsik
authors.initials: I
authors.lastname: Pe'er
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, United States of America.|Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Di Paolo
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, United States of America.|Department of Neurology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Roy N
authors.identifier: http://orcid.org/0000-0002-5717-4875
authors.initials: RN
authors.lastname: Alcalay
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005679:G(M3) Ganglioside / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood* / Q000503:physiopathology; D012727:Sex Characteristics
chemical_list: D015415:Biomarkers; D005679:G(M3) Ganglioside