{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:24:34Z","timestamp":1791498274764,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"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>The fact that Parkinson\u2019s disease (PD) pathologies are well advanced in most PD patients by the time of clinical elucidation attests to the importance of early diagnosis. Our attempt to achieve this has capitalized on our previous finding that GM1 ganglioside is expressed at subnormal levels in virtually all tissues of sporadic PD (sPD) patients including blood cells. GM1 is present in most vertebrate cells, is especially abundant in neurons where it was shown essential for their effective functioning and long term viability. We have utilized peripheral blood mononuclear cells (PBMCs) which, despite their low GM1, we found to be significantly lower in sPD patients compared to age-matched healthy controls. To quantify GM1 (and GD1a) we used high performance thin-layer chromatography combined with cholera toxin B linked to horseradish peroxidase, followed by densitometric quantification. GM1 was also deficient in PBMCs from PD patients with mutations in the glucocerebrosidase gene (PD-GBA), apparently even lower than in sPD. Reasons are given why we believe these results obtained with patients manifesting fully developed PD will apply as well to PD patients in preclinical stages\u2014a topic for future study. We also suggest that these findings point to a potential disease altering therapy for PD once the early diagnosis is established.<\/jats:p>","DOI":"10.3390\/ijms222111522","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T23:54:33Z","timestamp":1635292473000},"page":"11522","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Subnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson\u2019s Disease?"],"prefix":"10.3390","volume":"22","author":[{"given":"Samar K.","family":"Alselehdar","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Physiology, and Neuroscience, Rutgers, The State University of NJ, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monami","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Neuroscience, Rutgers, The State University of NJ, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Neuroscience, Rutgers, The State University of NJ, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy N.","family":"Alcalay","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Surface","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Ledeen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Neuroscience, Rutgers, The State University of NJ, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.3233\/JPD-181474","article-title":"The Emerging Evidence of the Parkinson Pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J. Parkinsons Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.bbr.2009.12.048","article-title":"The cholinergic system and Parkinson disease","volume":"221","author":"Bohnen","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3389\/fphar.2020.593822","article-title":"The noradrenergic system in Parkinson\u2019s disease","volume":"11","author":"Miguelez","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.bbr.2014.07.037","article-title":"Serotonin in Parkinson\u2019s disease","volume":"277","author":"Politis","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1111\/cns.13429","article-title":"Development of early diagnosis of Parkinson\u2019s disease: Illusion or reality?","volume":"26","author":"Ugrumov","year":"2020","journal-title":"CNS Neurosci. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.tibs.2015.04.005","article-title":"The multi-tasked life of GM1 ganglioside, a true factotum of nature","volume":"40","author":"Ledeen","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chiricozzi, E., Lunghi, G., Di Biase, E., Fazzari, M., Sonnino, S., and Mauri, L. (2020). GM1 ganglioside is a key factor in maintaining the mammalian neuronal functions avoiding neurodegeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030868"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ledeen, R.W., Chowdhury, S., Lu, Z.H., Chakraborty, M., and Wu, G. (2021). Systemic deficiency of GM1 ganglioside in Parkinson\u2019s disease tissues and its relation to the disease etiology. Glycoconj. J., in press.","DOI":"10.1007\/s10719-021-10025-9"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/ene.13837","article-title":"Neurological effects of glucocerebrosidase gene mutations","volume":"26","author":"Mullin","year":"2019","journal-title":"Eur. J. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1093\/brain\/awv179","article-title":"Glucocerebrosidase activity in Parkinson\u2019s disease with and without GBA mutation","volume":"135","author":"Alcalay","year":"2015","journal-title":"Brain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1093\/glycob\/11.10.831","article-title":"The major gangliosides of human peripheral blood monocytes\/macrophages: Absence of ganglio series structures","volume":"11","author":"Yohe","year":"2001","journal-title":"Glycobiology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.2337\/db10-1309","article-title":"Ganglioside GM1 deficiency in effector T cells from NOD mice induces resistance to regulatory T-cell suppression","volume":"60","author":"Wu","year":"2011","journal-title":"Diabetes"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-1-4939-8552-4_2","article-title":"Gangliosides of the Nervous System","volume":"Volume 1804","author":"Sonnino","year":"2018","journal-title":"Methods in Molecular Biology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/bs.pmbts.2017.12.009","article-title":"Gangliosides, \u03b1-Synuclein, and Parkinson\u2019s disease","volume":"Volume 156","author":"Schnaar","year":"2018","journal-title":"Progress in Molecular Biology and Translational Science: Gangliosides in Health and Disease"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.expneurol.2014.10.010","article-title":"GDNF signaling implemented by GM1 ganglioside; failure in Parkinson\u2019s disease and GM1-deficient murine model","volume":"263","author":"Hadaczek","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/nn.2136","article-title":"Absolute requirement of GDNF for adult catecholaminergic neuron survival","volume":"11","author":"Pascual","year":"2008","journal-title":"Nat. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1073\/pnas.92.11.5087","article-title":"Ganglioside GM1 binds to the Trk protein and regulates receptor function","volume":"92","author":"Mutoh","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0014-5793(98)01344-1","article-title":"Influence of endogenous GM1 ganglioside on TrkB activity in cultured neurons","volume":"439","author":"Pitto","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1021\/bi061749a","article-title":"GM1 specifically interacts with \u03b1-synuclein and inhibits fibrillation","volume":"46","author":"Martinez","year":"2007","journal-title":"Biochemistry"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Bartels, T., Kim, N.C., Luth, E.S., and Selkoe, D.J. (2014). N-Alpha-acetylation of \u03b1-synuclein increases its helical folding propensity, GM1 binding specificity and resistance to aggregation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103727"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1002\/jnr.23090","article-title":"Deficiency of ganglioside GM1 correlates with Parkinson\u2019s disease in mice and humans","volume":"90","author":"Wu","year":"2012","journal-title":"J. Neurosci. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8362","DOI":"10.1038\/s41598-019-42847-x","article-title":"GM1 ganglioside modifies \u03b1-synuclein toxicity and is neuroprotective in a rat \u03b1-synuclein model of Parkinson\u2019s disease","volume":"9","author":"Schneider","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"145","DOI":"10.2147\/nedt.2007.3.1.145","article-title":"Prodromal non-motor symptoms of Parkinson\u2019s disease","volume":"3","author":"Pellicano","year":"2007","journal-title":"Neuropsych. Dis. Treat."},{"key":"ref_24","unstructured":"Haliday, G.M., Barker, R.A., and Rowe, D.B. (2011). Non-Dopamine Lesions in Parkinson\u2019s Disease, Oxford University Press."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.neuroscience.2018.11.034","article-title":"Loss of enzyme activity in mutated B4GALNT1 gene products in patients with Hereditary Spastic Paraplegia results in relatively mild neurological disorders: Similarity with phenotypes of B4galnt1 knockout mice","volume":"397","author":"Bhuiyan","year":"2019","journal-title":"Neuroscience"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S1474-4422(19)30320-5","article-title":"Identification of novel risk loci, causal insights, and heritable risk for Parkinson\u2019s disease: A meta-analysis of genome-wide association studies","volume":"18","author":"Nalls","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Schneider, J. (2018). Altered expression of genes involved in ganglioside biosynthesis in substantia nigra neurons in Parkinson\u2019s disease. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199189"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/jnc.12456","article-title":"Epigenetic activation of mouse ganglioside synthase genes: Implications for neurogenesis","volume":"128","author":"Tsai","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s10719-016-9719-6","article-title":"Epigenetic regulation of ganglioside expression in neural stem cells and neuronal cells","volume":"34","author":"Itokazu","year":"2016","journal-title":"Glycoconj. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1046\/j.1471-4159.1994.63051802.x","article-title":"Membrane lipids of adult human brain: Lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years","volume":"63","author":"Svennerholm","year":"1994","journal-title":"J. Neurochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0005-2760(89)90175-6","article-title":"Human brain gangliosides: Developmental changes from early fetal stage to advanced age","volume":"1005","author":"Svennerholm","year":"1989","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1093\/glycob\/cws057","article-title":"Mammalian sialidases: Physiological and pathological roles in cellular functions","volume":"22","author":"Miyagi","year":"2012","journal-title":"Glycobiology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jns.2010.02.009","article-title":"GM1 ganglioside in Parkinson\u2019s disease: Results of a five-year open study","volume":"292","author":"Schneider","year":"2010","journal-title":"J. Neuro. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.jns.2012.10.024","article-title":"A randomized, controlled, delayed start trial of GM1 ganglioside in treated Parkinson\u2019s disease patients","volume":"324","author":"Schneider","year":"2013","journal-title":"J. Neurol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"113284","DOI":"10.1016\/j.expneurol.2020.113284","article-title":"Mice deficient in GM1 manifest both motor and non-motor symptoms of Parkinson\u2019s disease; successful treatment with synthetic GM1 ganglioside","volume":"329","author":"Wu","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1097\/00001756-199909290-00006","article-title":"Reduced dopamine in peripheral blood lymphocytes in Parkinson\u2019s disease","volume":"10","author":"Caronti","year":"1999","journal-title":"Neuroreport"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s007020170030","article-title":"Dopamine transporter immunoreactivity in peripheral blood lymphocytes in Parkinson\u2019s disease","volume":"108","author":"Caronti","year":"2001","journal-title":"J. Neural Trans."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13024-019-0339-z","article-title":"Reduced sphingolipid hydrolase activities, substrate accumulation and ganglioside decline in Parkinson\u2019s disease","volume":"14","author":"Huebecker","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"623","DOI":"10.3233\/JPD-191786","article-title":"An assessment of LRRK2 serine 935 phosphorylation in human peripheral blood mononuclear cells in idiopathic Parkinson\u2019s disease and G2019S LRRK2 cohorts","volume":"10","author":"Padmanabhan","year":"2020","journal-title":"J. Parkinson\u2019s Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/0003-2697(72)90291-6","article-title":"Modification of the Lowry procedure for the analysis of proteolipid protein","volume":"47","author":"Lees","year":"1972","journal-title":"Anal. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1134\/S1061934816080116","article-title":"Application of thin-layer chromatography image analysis technique in quantitative determination of sphingomyelin","volume":"71","author":"Skowron","year":"2016","journal-title":"J. Anal. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3","article-title":"Index for Rating Diagnostic Tests","volume":"3","author":"Youden","year":"1950","journal-title":"Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1097\/01.ede.0000147512.81966.ba","article-title":"Optimal cut-point and its corresponding Youden index to discriminate individuals using pooled blood samples","volume":"16","author":"Schisterman","year":"2005","journal-title":"Epidemiology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11522\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:23:37Z","timestamp":1760167417000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,26]]},"references-count":43,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222111522"],"URL":"https:\/\/doi.org\/10.3390\/ijms222111522","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,26]]}}}