{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:56:23Z","timestamp":1792166183167,"version":"4.4.0"},"reference-count":108,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Biomarkers are molecules that can be used to observe changes in an individual\u2019s biochemical or medical status and provide information to aid diagnosis or treatment decisions. Dysregulation in lipid metabolism in the brain is a major risk factor for many neurodegenerative disorders, including frontotemporal dementia, Alzheimer\u2019s disease, Parkinson\u2019s disease, and amyotrophic lateral sclerosis. Thus, there is a growing interest in using lipids as biomarkers in neurodegenerative diseases, with the anionic phospholipid bis(monoacylglycerol)phosphate and (glyco-)sphingolipids being the most promising lipid classes thus far. In this review, we provide a general overview of lipid biology, provide examples of abnormal lysosomal lipid metabolism in neurodegenerative diseases, and discuss how these insights might offer novel and promising opportunities in biomarker development and therapeutic discovery. Finally, we discuss the challenges and opportunities of lipid biomarkers and biomarker panels in diagnosis, prognosis, and\/or treatment response in the clinic.<\/jats:p>","DOI":"10.3390\/ijms25010131","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T05:36:12Z","timestamp":1703136972000},"page":"131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Lipids as Emerging Biomarkers in Neurodegenerative Diseases"],"prefix":"10.3390","volume":"25","author":[{"given":"Justin","family":"Wei","sequence":"first","affiliation":[{"name":"Prevail Therapeutics, a Wholly Owned Subsidiary of Eli Lilly and Company, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Chin","family":"Wong","sequence":"additional","affiliation":[{"name":"Prevail Therapeutics, a Wholly Owned Subsidiary of Eli Lilly and Company, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Boland","sequence":"additional","affiliation":[{"name":"Prevail Therapeutics, a Wholly Owned Subsidiary of Eli Lilly and Company, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1194\/jlr.R800095-JLR200","article-title":"Update of the LIPID MAPS comprehensive classification system for lipids","volume":"50","author":"Fahy","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0022-2275(20)39619-X","article-title":"Lipid composition of the normal human brain: Gray matter, white matter, and myelin","volume":"6","author":"Sampson","year":"1965","journal-title":"J. Lipid Res."},{"key":"ref_3","first-page":"51","article-title":"Lipids in the nervous system: From biochemistry and molecular biology to patho-physiology","volume":"1851","author":"Cermenati","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S97","DOI":"10.1194\/jlr.R800073-JLR200","article-title":"Sphingolipidomics: A valuable tool for understanding the roles of sphingolipids in biology and disease","volume":"50","author":"Merrill","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/978-3-030-21162-2_7","article-title":"Sphingolipids as Biomarkers of Disease","volume":"1159","author":"Matanes","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1093\/eurheartj\/ehw148","article-title":"Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol","volume":"37","author":"Laaksonen","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1161\/ATVBAHA.116.307497","article-title":"Circulating Ceramides Predict Cardiovascular Outcomes in the Population-Based FINRISK 2002 Cohort","volume":"36","author":"Havulinna","year":"2016","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1161\/ATVBAHA.118.311199","article-title":"Plasma Ceramides","volume":"38","author":"Meeusen","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Bio."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Simons, K., and Sampaio, J.L. (2011). Membrane Organization and Lipid Rafts. Cold Spring Harb. Perspect. Biol., 3.","DOI":"10.1101\/cshperspect.a004697"},{"key":"ref_10","first-page":"121","article-title":"Membrane lipids as signaling molecules","volume":"18","author":"Fernandis","year":"2007","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.chembiol.2018.05.003","article-title":"Protein Lipidation in Cell Signaling and Diseases: Function, Regulation, and Therapeutic Opportunities","volume":"25","author":"Chen","year":"2018","journal-title":"Cell Chem. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/42408","article-title":"Functional rafts in cell membranes","volume":"387","author":"Simons","year":"1997","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15712","DOI":"10.1021\/jp108361d","article-title":"Structure, Dynamics, and Energetics of Lysobisphosphatidic Acid (LBPA) Isomers","volume":"114","author":"Goursot","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"a016816","DOI":"10.1101\/cshperspect.a016816","article-title":"Lipid Sorting and Multivesicular Endosome Biogenesis","volume":"5","author":"Bissig","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_15","unstructured":"Thudichum, J.L.F. (1884). A Treatise on the Chemical Constitution of the Brain: Based Throughout upon Original Researches, Bailli\u00e8re, Tindall, and Cox."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hannich, J.T., Umebayashi, K., and Riezman, H. (2011). Distribution and Functions of Sterols and Sphingolipids. Cold Spring Harb. Perspect. Biol., 3.","DOI":"10.1101\/cshperspect.a004762"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nrm.2017.138","article-title":"Understanding the diversity of membrane lipid composition","volume":"19","author":"Harayama","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.cell.2010.11.033","article-title":"Lipidomics: New Tools and Applications","volume":"143","author":"Wenk","year":"2010","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3390\/metabo2010019","article-title":"Mass spectrometry based lipidomics: An overview of techno-logical platforms","volume":"2","author":"Fauland","year":"2012","journal-title":"Metabolites"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/nmeth.4470","article-title":"Deciphering lipid structures based on platform-independent decision rules","volume":"14","author":"Hartler","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14054","DOI":"10.1021\/acs.analchem.0c03016","article-title":"Automated Annotation of Sphingolipids Including Accurate Identification of Hydroxylation Sites Using MSn Data","volume":"92","author":"Hartler","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8800","DOI":"10.1021\/acs.analchem.7b01126","article-title":"LipidHunter Identifies Phospholipids by High-Throughput Processing of LC-MS and Shotgun Lipidomics Datasets","volume":"89","author":"Ni","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Herzog, R., Schwudke, D., Schuhmann, K., Sampaio, J.L., Bornstein, S.R., Schroeder, M., and Shevchenko, A. (2011). A novel informatics concept for high-throughput shotgun lipidomics based on the molecular fragmentation query language. Genome Biol., 12.","DOI":"10.1186\/gb-2011-12-1-r8"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Koelmel, J.P., Kroeger, N.M., Ulmer, C.Z., Bowden, J.A., Patterson, R.E., Cochran, J.A., Beecher, C.W.W., Garrett, T.J., and Yost, R.A. (2017). LipidMatch: An automated workflow for rule-based lipid identification using untargeted high-resolution tandem mass spectrometry data. BMC Bioinform., 18.","DOI":"10.1186\/s12859-017-1744-3"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/s41587-020-0531-2","article-title":"A lipidome atlas in MS-DIAL 4","volume":"38","author":"Tsugawa","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4771","DOI":"10.1038\/s41467-021-24984-y","article-title":"Quality control requirements for the correct annotation of lipidomics data","volume":"12","author":"Eichmann","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100138","DOI":"10.1016\/j.jlr.2021.100138","article-title":"Recommendations for good practice in MS-based lipidomics","volume":"62","author":"Ahrends","year":"2021","journal-title":"J. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lipidomics Standards Initiative Consortium (2019). Lipidomics needs more standardization. Nat. Metab., 1, 745\u2013747.","DOI":"10.1038\/s42255-019-0094-z"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1194\/jlr.M033506","article-title":"Shorthand notation for lipid structures derived from mass spectrometry","volume":"54","author":"Liebisch","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1194\/jlr.S120001025","article-title":"Update on LIPID MAPS classification, nomenclature, and shorthand notation for MS-derived lipid structures","volume":"61","author":"Liebisch","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1038\/s42255-022-00628-3","article-title":"Introducing the Lipidomics Minimal Reporting Checklist","volume":"4","author":"McDonald","year":"2022","journal-title":"Nat. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/mas.21492","article-title":"Selection of internal standards for accurate quantification of complex lipid species in biological extracts by electrospray ionization mass spectrometry\u2014What, how and why?","volume":"36","author":"Wang","year":"2017","journal-title":"Mass Spectrom. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/y59-099","article-title":"A rapid method of total lipid extraction and purification","volume":"37","author":"Bligh","year":"1959","journal-title":"Can. J. Biochem. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1194\/jlr.D700041-JLR200","article-title":"Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics","volume":"49","author":"Matyash","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1039\/a905904k","article-title":"Determination of total lipid using non-chlorinated solvents","volume":"124","author":"Smedes","year":"1999","journal-title":"Analyst"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/0003-2697(78)90046-5","article-title":"Lipid extraction of tissues with a low-toxicity solvent","volume":"90","author":"Hara","year":"1978","journal-title":"Anal. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.chroma.2014.04.070","article-title":"Quantitation of phosphatidic acid and lysophosphatidic acid molecular species using hydrophilic interaction liquid chromatography coupled to electrospray ionization high resolution mass spectrometry","volume":"1347","author":"Triebl","year":"2014","journal-title":"J. Chromatogr. A"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Saini, R.K., Prasad, P., Shang, X., and Keum, Y.S. (2021). Advances in Lipid Extraction Methods\u2014A Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413643"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.addr.2020.04.009","article-title":"Sphingolipids as prognostic biomarkers of neurodegeneration, neuroinflammation, and psychiatric diseases and their emerging role in lipidomic investigation methods","volume":"159","author":"Luo","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1016\/j.bbamem.2006.06.009","article-title":"Sphingolipid metabolism in neural cells","volume":"1758","author":"Herget","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Maxfield, F.R. (2016). Lysosomes: Biology, Diseases, and Therapeutics, Wiley.","DOI":"10.1002\/9781118978320"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1007\/s11064-010-0337-6","article-title":"Biological Function of the Cellular Lipid BMP\u2014BMP as a Key Activator for Cholesterol Sorting and Membrane Digestion","volume":"36","author":"Gallala","year":"2011","journal-title":"Neurochem. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5924","DOI":"10.1038\/s41467-022-33500-9","article-title":"Deficiency of the frontotemporal dementia gene GRN results in gangliosidosis","volume":"13","author":"Boland","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_45","first-page":"25","article-title":"Modulating lysosomal pH: A molecular and nanoscale materials design perspective","volume":"2","author":"Zeng","year":"2020","journal-title":"JoLS J. Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1042\/BJ20071043","article-title":"Effect of lysosomal storage on bis(monoacylglycero)phosphate","volume":"411","author":"Meikle","year":"2008","journal-title":"Biochem. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev.cellbio.21.122303.120013","article-title":"Principles of lysosomal membrane digestion: Stimulation of sphingolipid degradation by sphin-golipid activator proteins and anionic lysosomal lipids","volume":"21","author":"Kolter","year":"2005","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.1002\/1873-3468.13114","article-title":"Emerging concepts of ganglioside metabolism","volume":"592","author":"Sandhoff","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.tcb.2022.09.006","article-title":"Lysosomal functions of progranulin and implications for treatment of frontotemporal dementia","volume":"33","author":"Simon","year":"2023","journal-title":"Trends Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1007\/s12031-011-9538-y","article-title":"Estimating the number of persons with frontotemporal lobar degeneration in the US population","volume":"45","author":"Knopman","year":"2011","journal-title":"J. Mol. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1038\/nature05016","article-title":"Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17","volume":"442","author":"Baker","year":"2006","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1038\/nature05017","article-title":"Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21","volume":"442","author":"Cruts","year":"2006","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4651","DOI":"10.1016\/j.cell.2021.08.002","article-title":"Rescue of a lysosomal storage disorder caused by Grn loss of function with a brain penetrant progranulin biologic","volume":"184","author":"Logan","year":"2021","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Root, J., Mendsaikhan, A., Nandy, S., Taylor, G., Wang, M., Araujo, L.T., Merino, P., Ryu, D., Holler, C., and Thompson, B.M. (2023, November 13). Granulins Rescue Inflammation, Lysosome Dysfunction, and Neuropathology in a Mouse Model of Progranulin Deficiency. Available online: https:\/\/www.biorxiv.org\/content\/10.1101\/2023.04.17.536004v1.","DOI":"10.1101\/2023.04.17.536004"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1038\/s41467-018-03844-2","article-title":"Structural basis for the activation of acid ceramidase","volume":"9","author":"Gebai","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"35814","DOI":"10.1074\/jbc.M006568200","article-title":"Degradation of membrane-bound ganglioside GM1. Stimulation by bis(monoacylglycero)phosphate and the activator proteins SAP-B and GM2-AP","volume":"275","author":"Wilkening","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1042\/bj3030377","article-title":"Analysis of glucocerebrosidase activity using N-(1-[14C]hexanoyl)-D-erythroglucosylsphingosine demonstrates a correlation between levels of residual enzyme activity and the type of Gaucher disease","volume":"303","author":"Horowitz","year":"1994","journal-title":"Biochem. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1432-1033.1994.tb18844.x","article-title":"Hydrolysis of lactosylceramide by human galactosylceramidase and GM1-\u03b2-galactosidase in a detergent-free system and its stimulation by sphingolipid activator proteins, sap-B and sap-C. Ac-tivator proteins stimulate lactosylceramide hydrolysis","volume":"222","author":"Zschoche","year":"1994","journal-title":"Eur. J. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/nature08710","article-title":"Hsp70 stabilizes lysosomes and reverts Niemann\u2013Pick disease-associated lysosomal pathology","volume":"463","author":"Kirkegaard","year":"2010","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1002\/(SICI)1521-3773(19990601)38:11<1532::AID-ANIE1532>3.0.CO;2-U","article-title":"Sphingolipids\u2014Their Metabolic pathways and the pathobiochemistry of neurodegenerative diseases","volume":"38","author":"Kolter","year":"1999","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1750-1326-4-9","article-title":"\u03b1-Synuclein and neuronal cell death","volume":"4","author":"Cookson","year":"2009","journal-title":"Mol. Neurodegener."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Riboldi, G.M., and Di Fonzo, A.B. (2019). GBA, Gaucher Disease, and Parkinson\u2019s Disease: From Genetic to Clinic to New Therapeutic Approaches. Cells, 8.","DOI":"10.3390\/cells8040364"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1093\/brain\/awu002","article-title":"Glucocerebrosidase is shaking up the synucleinopathies","volume":"137","author":"Siebert","year":"2014","journal-title":"Brain"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1056\/NEJMoa0901281","article-title":"Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson\u2019s Disease","volume":"361","author":"Sidransky","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cell.2011.06.001","article-title":"Gaucher disease glucocerebrosidase and \u03b1-synuclein form a bidirectional pathogenic loop in synucle-inopathies","volume":"146","author":"Mazzulli","year":"2011","journal-title":"Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.conb.2021.11.004","article-title":"GBA mutations, glucosylceramide and Parkinson\u2019s disease","volume":"72","author":"Milenkovic","year":"2022","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Alselehdar, S.K., Chakraborty, M., Chowdhury, S., Alcalay, R.N., Surface, M., and Ledeen, R. (2021). Subnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson\u2019s Disease?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111522"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Chowdhury, S., and Ledeen, R. (2022). The Key Role of GM1 Ganglioside in Parkinson\u2019s Disease. Biomolecules, 12.","DOI":"10.3390\/biom12020173"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"306","DOI":"10.3389\/fnhum.2019.00306","article-title":"G2019S Variation in LRRK2: An Ideal Model for the Study of Parkinson\u2019s Disease?","volume":"13","author":"Ren","year":"2019","journal-title":"Front. Hum. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1126\/scitranslmed.aaa3634","article-title":"Effect of selective LRRK2 kinase inhibition on nonhuman primate lung","volume":"7","author":"Fuji","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/mds.27818","article-title":"Higher Urine bis(Monoacylglycerol)Phosphate Levels in LRRK2 G2019S Mutation Carriers: Implications for Therapeutic Development","volume":"35","author":"Alcalay","year":"2020","journal-title":"Mov. Disord."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"eabj2658","DOI":"10.1126\/scitranslmed.abj2658","article-title":"Preclinical and clinical evaluation of the LRRK2 inhibitor DNL201 for Parkinson\u2019s disease","volume":"14","author":"Jennings","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1080\/10245332.2016.1240391","article-title":"Gaucher disease epidemiology and natural history: A comprehensive review of the literature","volume":"22","author":"Nalysnyk","year":"2017","journal-title":"Hematology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1002\/jimd.12235","article-title":"The definition of neuronopathic Gaucher disease","volume":"43","author":"Schiffmann","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/S0140-6736(08)61522-6","article-title":"Phenotype, diagnosis, and treatment of Gaucher\u2019s disease","volume":"372","author":"Grabowski","year":"2008","journal-title":"Lancet"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jalz.2018.06.3063","article-title":"Racial and ethnic estimates of Alzheimer\u2019s disease and related dementias in the United States (2015\u20132060) in adults aged \u226565 years","volume":"15","author":"Matthews","year":"2019","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"311","DOI":"10.3233\/JAD-2010-1221","article-title":"Alzheimer\u2019s disease and the amyloid-beta peptide","volume":"19","author":"Murphy","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1038\/nm1095-1062","article-title":"GM1 ganglioside-bound amyloid beta-protein (A beta): A possible form of preamyloid in Alzheimer\u2019s disease","volume":"1","author":"Yanagisawa","year":"1995","journal-title":"Nat. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1021\/bi982345o","article-title":"Interactions of amyloid beta-peptide (1\u201340) with ganglioside-containing membranes","volume":"38","author":"Matsuzaki","year":"1999","journal-title":"Biochemistry"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"22987","DOI":"10.1074\/jbc.272.37.22987","article-title":"Acceleration of amyloid fibril formation by specific binding of Abeta-(1\u201340) peptide to ganglioside-containing membrane vesicles","volume":"272","author":"Glabe","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1111\/j.1471-4159.2005.03444.x","article-title":"Cross-seeding of wild-type and hereditary variant-type amyloid beta-proteins in the presence of gangliosides","volume":"95","author":"Yamamoto","year":"2005","journal-title":"J. Neurochem."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Matsuzaki, K. (2020). A\u03b2-ganglioside interactions in the pathogenesis of Alzheimer\u2019s disease. Biochim. Biophys. Acta Biomembr., 1862.","DOI":"10.1016\/j.bbamem.2020.183233"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1093\/brain\/aww015","article-title":"Cerebrospinal fluid analysis detects cerebral amyloid-\u03b2 accumulation earlier than positron emission tomography","volume":"139","author":"Palmqvist","year":"2016","journal-title":"Brain"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.neulet.2012.04.019","article-title":"Elevated cerebrospinal fluid sphingomyelin levels in prodromal Alzheimer\u2019s disease","volume":"516","author":"Kosicek","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_85","first-page":"e12008","article-title":"Plasma Lipids as Biomarkers for Alzheimer\u2019s Disease: A Systematic Review","volume":"12","author":"Agarwal","year":"2020","journal-title":"Cureus"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Kao, Y.C., Ho, P.C., Tu, Y.K., Jou, I.M., and Tsai, K.J. (2020). Lipids and Alzheimer\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041505"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/nrn3012","article-title":"Linking lipids to Alzheimer\u2019s disease: Cholesterol and beyond","volume":"12","author":"Kim","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"303","DOI":"10.2174\/1567205014666170505101426","article-title":"Lipid Biomarkers in Alzheimer\u2019s Disease","volume":"15","author":"Zarrouk","year":"2018","journal-title":"Curr. Alzheimer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1111\/ejn.12169","article-title":"Autophagy failure in Alzheimer\u2019s disease and the role of defective lysosomal acidification","volume":"37","author":"Wolfe","year":"2013","journal-title":"Eur. J. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/s41586-022-05439-w","article-title":"APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes","volume":"611","author":"Blanchard","year":"2022","journal-title":"Nature"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"eaaz4564","DOI":"10.1126\/scitranslmed.aaz4564","article-title":"APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia","volume":"13","author":"Sienski","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"10565","DOI":"10.1073\/pnas.1913956117","article-title":"Inhibition of sphingolipid synthesis improves outcomes and survival in GARP mutant wobbler mice, a model of motor neuron degeneration","volume":"117","author":"Petit","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"8100","DOI":"10.1073\/pnas.1508767112","article-title":"Glycosphingolipids are modulators of disease pathogenesis in amyotrophic lateral sclerosis","volume":"112","author":"Dodge","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"13562","DOI":"10.1038\/s41598-021-92112-3","article-title":"Lipidomics study of plasma from patients suggest that ALS and PLS are part of a continuum of motor neuron disorders","volume":"11","author":"Larrea","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"17652","DOI":"10.1038\/s41598-017-17389-9","article-title":"Lipidomics Reveals Cerebrospinal-Fluid Signatures of ALS","volume":"7","author":"Blasco","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Blasco, H., Patin, F., Descat, A., Gar\u00e7on, G., Corcia, P., Gel\u00e9, P., Lenglet, T., Bede, P., Meininger, V., and Devos, D. (2018). A pharmaco-metabolomics approach in a clinical trial of ALS: Identification of predictive markers of progression. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198116"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Podbielska, M., O\u2019keeffe, J., and Pokryszko-Dragan, A. (2021). New Insights into Multiple Sclerosis Mechanisms: Lipids on the Track to Control Inflammation and Neurodegeneration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147319"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"639757","DOI":"10.3389\/fendo.2021.639757","article-title":"Disrupted Lipid Metabolism in Multiple Sclerosis: A Role for Liver X Receptors?","volume":"12","author":"Siddique","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"106983","DOI":"10.1016\/j.ymgme.2022.106983","article-title":"Plasma GM2 ganglioside potential biomarker for diagnosis, prognosis and disease monitoring of GM2-Gangliosidosis","volume":"138","author":"Blondel","year":"2023","journal-title":"Mol. Genet. Metab."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Kodama, T., Togawa, T., Tsukimura, T., Kawashima, I., Matsuoka, K., Kitakaze, K., Tsuji, D., Itoh, K., Ishida, Y.-I., and Suzuki, M. (2011). Lyso-GM2 Ganglioside: A Possible Biomarker of Tay-Sachs Disease and Sandhoff Disease. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0029074"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ymgme.2016.12.008","article-title":"Types A and B Niemann-Pick disease","volume":"120","author":"Schuchman","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1034\/j.1399-0004.2003.00147.x","article-title":"Niemann-Pick disease type C","volume":"64","author":"Vanier","year":"2003","journal-title":"Clin. Genet."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/brain\/awac379","article-title":"Venglustat combined with imiglucerase for neurological disease in adults with Gaucher disease type 3: The LEAP trial","volume":"146","author":"Schiffmann","year":"2023","journal-title":"Brain"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"101030","DOI":"10.1016\/j.plipres.2020.101030","article-title":"Lipid-based biomarkers for CVD, COPD, and aging\u2014A translational perspective","volume":"78","author":"Ekroos","year":"2020","journal-title":"Prog. Lipid Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.pcad.2022.11.004","article-title":"The associations between exercise and lipid biomarkers","volume":"75","author":"Sulague","year":"2022","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_106","first-page":"747","article-title":"Reporting of lipidomics data should be standardized","volume":"1862","author":"Liebisch","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids"},{"key":"ref_107","unstructured":"World Health Organization (2023, December 04). Global Action Plan on the Public Health Response to Dementia 2017\u20132025, Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/259615\/9789241513487-eng.pdf?sequence=1."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"7319","DOI":"10.1073\/pnas.1701597114","article-title":"Poor caregiver mental health predicts mortality of patients with neurodegenerative disease","volume":"114","author":"Lwi","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/1\/131\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:39:29Z","timestamp":1760132369000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/1\/131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,21]]},"references-count":108,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25010131"],"URL":"https:\/\/doi.org\/10.3390\/ijms25010131","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,21]]}}}