{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:40:44Z","timestamp":1792701644504,"version":"4.5.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":98,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Clinical Research Special Project for High-Level Hospital Construction in Jiangsu Province","award":["LCZX202513"],"award-info":[{"award-number":["LCZX202513"]}]},{"DOI":"10.13039\/501100018636","name":"Xuzhou Science and Technology Program","doi-asserted-by":"publisher","award":["KC25064"],"award-info":[{"award-number":["KC25064"]}],"id":[{"id":"10.13039\/501100018636","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Paired Assistance Research Project of The Affiliated Hospital of Xuzhou Medical University","award":["SHJDBF2024206"],"award-info":[{"award-number":["SHJDBF2024206"]}]},{"name":"XZHMU-QL Joint Research Fund","award":["QL-YB077"],"award-info":[{"award-number":["QL-YB077"]}]},{"name":"Special Funding for Overseas Research and Training for Staff of the Affiliated Hospital of Xuzhou Medical University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Parkinsons Dis."],"DOI":"10.1038\/s41531-026-01479-5","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T14:39:05Z","timestamp":1784212745000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma ceramide ratios define metabolic\u2013inflammatory associations with cognitive impairment in Parkinson\u2019s disease"],"prefix":"10.1038","volume":"12","author":[{"given":"Nuan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congxin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishun","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingwei","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"1479_CR1","doi-asserted-by":"crossref","unstructured":"Aarsland, D. et al. Parkinson disease-associated cognitive impairment. Nat. Rev. Dis. Primers. 7, 47 (2021).","DOI":"10.1038\/s41572-021-00280-3"},{"key":"1479_CR2","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/S1474-4422(21)00330-6","volume":"21","author":"D Weintraub","year":"2022","unstructured":"Weintraub, D. et al. The neuropsychiatry of Parkinson\u2019s disease: advances and challenges. Lancet Neurol. 21, 89\u2013102 (2022).","journal-title":"Lancet Neurol."},{"key":"1479_CR3","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1007\/s00401-021-02367-3","volume":"142","author":"M Kurzawa-Akanbi","year":"2021","unstructured":"Kurzawa-Akanbi, M. et al. Altered ceramide metabolism is a feature in the extracellular vesicle-mediated spread of alpha-synuclein in Lewy body disorders. Acta Neuropathol. 142, 961\u2013984 (2021).","journal-title":"Acta Neuropathol."},{"key":"1479_CR4","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.molmed.2018.10.009","volume":"25","author":"J Kurz","year":"2019","unstructured":"Kurz, J., Parnham, M., Geisslinger, G. & Schiffmann, S. Ceramides as novel disease biomarkers. Trends Mol. Med. 25, 20\u201332 (2019).","journal-title":"Trends Mol. Med."},{"key":"1479_CR5","doi-asserted-by":"publisher","first-page":"100955","DOI":"10.1016\/j.jlr.2025.100955","volume":"67","author":"Y Peng","year":"2026","unstructured":"Peng, Y., Chen, S., Li, J., Lin, C. & Kuo, C. Dysregulated metabolism of ceramides and glycosphingolipids in Parkinson\u2019s disease. J. Lipid Res. 67, 100955 (2026).","journal-title":"J. Lipid Res."},{"key":"1479_CR6","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1093\/brain\/awt367","volume":"137","author":"K Murphy","year":"2014","unstructured":"Murphy, K. et al. Reduced glucocerebrosidase is associated with increased \u03b1-synuclein in sporadic Parkinson\u2019s disease. Brain 137, 834\u2013848 (2014).","journal-title":"Brain"},{"key":"1479_CR7","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/s41531-023-00517-w","volume":"9","author":"C Leyns","year":"2023","unstructured":"Leyns, C. et al. Glucocerebrosidase activity and lipid levels are related to protein pathologies in Parkinson\u2019s disease. Npj Parkinsons Dis. 9, 74 (2023).","journal-title":"Npj Parkinsons Dis."},{"key":"1479_CR8","first-page":"346783","volume":"2015","author":"M Jembrek","year":"2015","unstructured":"Jembrek, M., Hof, P. & Simic, G. Ceramides in Alzheimer\u2019s disease: key mediators of neuronal apoptosis induced by oxidative stress and A\u03b2 accumulation. Oxid. Med. Cell Longev. 2015, 346783 (2015).","journal-title":"Oxid. Med. Cell Longev."},{"key":"1479_CR9","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1093\/brain\/awab371","volume":"145","author":"C Galvagnion","year":"2022","unstructured":"Galvagnion, C. et al. Sphingolipid changes in Parkinson L444P GBA mutation fibroblasts promote \u03b1-synuclein aggregation. Brain 145, 1038\u20131051 (2022).","journal-title":"Brain"},{"key":"1479_CR10","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1056\/NEJMoa0901281","volume":"361","author":"E Sidransky","year":"2009","unstructured":"Sidransky, E. et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson\u2019s disease. N. Engl. J. Med. 361, 1651\u20131661 (2009).","journal-title":"N. Engl. J. Med."},{"key":"1479_CR11","doi-asserted-by":"publisher","first-page":"4392","DOI":"10.1007\/s00415-024-12374-5","volume":"271","author":"C Chang","year":"2024","unstructured":"Chang, C., Tan, C., Hong, W. & Yu, R. GBA moderates cognitive reserve\u2019s effect on cognitive function in patients with Parkinson\u2019s disease. J. Neurol. 271, 4392\u20134405 (2024).","journal-title":"J. Neurol."},{"key":"1479_CR12","doi-asserted-by":"publisher","first-page":"eadk8249","DOI":"10.1126\/scisignal.adk8249","volume":"17","author":"R Wang","year":"2024","unstructured":"Wang, R. et al. Glucosylceramide accumulation in microglia triggers STING-dependent neuroinflammation and neurodegeneration in mice. Sci. Signal. 17, eadk8249 (2024).","journal-title":"Sci. Signal."},{"key":"1479_CR13","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/1750-1326-7-45","volume":"7","author":"T Martinez","year":"2012","unstructured":"Martinez, T., Chen, X., Bandyopadhyay, S., Merrill, A. & Tansey, M. Ceramide sphingolipid signaling mediates Tumor Necrosis Factor (TNF)-dependent toxicity via caspase signaling in dopaminergic neurons. Mol. Neurodegener. 7, 45 (2012).","journal-title":"Mol. Neurodegener."},{"key":"1479_CR14","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s12974-019-1436-1","volume":"16","author":"N de Wit","year":"2019","unstructured":"de Wit, N. et al. Astrocytic ceramide as possible indicator of neuroinflammation. J. Neuroinflamm. 16, 48 (2019).","journal-title":"J. Neuroinflamm."},{"key":"1479_CR15","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1111\/jnc.14225","volume":"143","author":"H Scheiblich","year":"2017","unstructured":"Scheiblich, H. et al. Activation of the NLRP3 inflammasome in microglia: the role of ceramide. J. Neurochem. 143, 534\u2013550 (2017).","journal-title":"J. Neurochem."},{"key":"1479_CR16","doi-asserted-by":"publisher","first-page":"168000","DOI":"10.1016\/j.jmb.2023.168000","volume":"435","author":"M Vos","year":"2023","unstructured":"Vos, M., Klein, C. & Hicks, A. Role of ceramides and sphingolipids in Parkinson\u2019s disease. J. Mol. Biol. 435, 168000 (2023).","journal-title":"J. Mol. Biol."},{"key":"1479_CR17","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.tem.2018.11.003","volume":"30","author":"G Lin","year":"2019","unstructured":"Lin, G., Wang, L., Marcogliese, P. & Bellen, H. Sphingolipids in the pathogenesis of Parkinson\u2019s disease and Parkinsonism. Trends Endocrinol. Met. 30, 106\u2013117 (2019).","journal-title":"Trends Endocrinol. Met."},{"key":"1479_CR18","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1002\/mds.28015","volume":"35","author":"R Wijeyekoon","year":"2020","unstructured":"Wijeyekoon, R. et al. Cerebrospinal fluid cytokines and neurodegeneration-associated proteins in Parkinson\u2019s disease. Mov. Disord. 35, 1062\u20131066 (2020).","journal-title":"Mov. Disord."},{"key":"1479_CR19","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/s41582-020-0344-4","volume":"16","author":"E Tan","year":"2020","unstructured":"Tan, E. et al. Parkinson disease and the immune system - associations, mechanisms and therapeutics. Nat. Rev. Neurol. 16, 303\u2013318 (2020).","journal-title":"Nat. Rev. Neurol."},{"key":"1479_CR20","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1186\/s40478-020-01083-5","volume":"8","author":"A Kouli","year":"2020","unstructured":"Kouli, A., Camacho, M., Allinson, K. & Williams-Gray, C. Neuroinflammation and protein pathology in Parkinson\u2019s disease dementia. Acta Neuropathol. Com. 8, 211 (2020).","journal-title":"Acta Neuropathol. Com."},{"key":"1479_CR21","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/s41577-022-00684-6","volume":"22","author":"M Tansey","year":"2022","unstructured":"Tansey, M. et al. Inflammation and immune dysfunction in Parkinson disease. Nat. Rev. Immunol. 22, 657\u2013673 (2022).","journal-title":"Nat. Rev. Immunol."},{"key":"1479_CR22","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/bpa.12344","volume":"27","author":"J Power","year":"2017","unstructured":"Power, J., Barnes, O. & Chegini, F. Lewy bodies and the mechanisms of neuronal cell death in Parkinson\u2019s disease and dementia with lewy bodies. Brain Pathol. 27, 3\u201312 (2017).","journal-title":"Brain Pathol."},{"key":"1479_CR23","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s40478-025-02014-y","volume":"13","author":"S Liu","year":"2025","unstructured":"Liu, S. et al. Oligodendrocyte-specific overexpression of human alpha-synuclein results in elevated MBP levels and inflammatory responses in TgM83 mice, mimicking the pathological features of multiple system atrophy. Acta Neuropathol. Com. 13, 94 (2025).","journal-title":"Acta Neuropathol. Com."},{"key":"1479_CR24","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s00415-025-13590-3","volume":"273","author":"Z Chen","year":"2025","unstructured":"Chen, Z., Mei, L. & Huang, Y. Multiple system atrophy: advances in pathogenesis and emerging therapeutic strategies. J. Neurol. 273, 49 (2025).","journal-title":"J. Neurol."},{"key":"1479_CR25","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1002\/glia.24329","volume":"71","author":"J Teo","year":"2023","unstructured":"Teo, J. et al. Early microglial response, myelin deterioration and lethality in mice deficient for very long chain ceramide synthesis in oligodendrocytes. Glia. 71, 1120\u20131141 (2023).","journal-title":"Glia."},{"key":"1479_CR26","doi-asserted-by":"crossref","unstructured":"Zhang, S. et al. Sensing ceramides by CYSLTR2 and P2RY6 to aggravate atherosclerosis. Nature 641 (2025).","DOI":"10.1038\/s41586-025-08792-8"},{"key":"1479_CR27","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.1007\/s12035-021-02688-0","volume":"59","author":"T Usenko","year":"2022","unstructured":"Usenko, T. et al. Impaired sphingolipid hydrolase activities in dementia with lewy bodies and multiple system atrophy. Mol. Neurobiol. 59, 2277\u20132287 (2022).","journal-title":"Mol. Neurobiol."},{"key":"1479_CR28","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1152\/physiol.2024.39.S1.424","volume":"39","author":"R Nicholson","year":"2024","unstructured":"Nicholson, R., Cedeno-Rosario, L., Li, Y. & Maschek, J. Ceramides as mediators of mitochondrial dysfunction driving kidney injury. Physiology 39, 424 (2024).","journal-title":"Physiology"},{"key":"1479_CR29","doi-asserted-by":"publisher","first-page":"156161","DOI":"10.1016\/j.metabol.2025.156161","volume":"166","author":"F Huang","year":"2025","unstructured":"Huang, F. et al. Ceramides increase mitochondrial permeabilization to trigger mtDNA-dependent inflammation in astrocytes during brain ischemia. Metabolism 166, 156161 (2025).","journal-title":"Metabolism"},{"key":"1479_CR30","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1007\/s10787-025-01719-9","volume":"33","author":"P Choudhary","year":"2025","unstructured":"Choudhary, P., Kumari, S., Bagri, K. & Deshmukh, R. Ceramide: a central regulator in Alzheimer\u2019s disease pathogenesis. Inflammopharmacology 33, 1775\u20131783 (2025).","journal-title":"Inflammopharmacology"},{"key":"1479_CR31","doi-asserted-by":"publisher","first-page":"101430","DOI":"10.1016\/j.redox.2020.101430","volume":"30","author":"E Afsar","year":"2020","unstructured":"Afsar, E. et al. Effect of ER stress on sphingolipid levels and apoptotic pathways in retinal pigment epithelial cells. Redox Biol. 30, 101430 (2020).","journal-title":"Redox Biol."},{"key":"1479_CR32","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1002\/glia.23153","volume":"65","author":"Q He","year":"2017","unstructured":"He, Q., Wang, Q., Yuan, C. & Wang, Y. Downregulation of miR-7116-5p in microglia by MPP1 sensitizes TNF-\u03b1 production to induce dopaminergic neuron damage. Glia 65, 1251\u20131263 (2017).","journal-title":"Glia"},{"key":"1479_CR33","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3389\/fnagi.2018.00129","volume":"10","author":"J Geng","year":"2018","unstructured":"Geng, J. et al. Blood-brain barrier disruption induced cognitive impairment is associated with increase of inflammatory cytokine. Front Aging Neurosci. 10, 129 (2018).","journal-title":"Front Aging Neurosci."},{"key":"1479_CR34","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/s12276-022-00789-x","volume":"54","author":"E Bae","year":"2022","unstructured":"Bae, E. et al. TNF-\u03b1 promotes \u03b1-synuclein propagation through stimulation of senescence-associated lysosomal exocytosis. Exp Mol. Med. 54, 788\u2013800 (2022).","journal-title":"Exp Mol. Med."},{"key":"1479_CR35","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/s41531-026-01263-5","volume":"12","author":"E Lee","year":"2026","unstructured":"Lee, E. et al. Inhibition of de novo ceramide synthesis mitigates alpha-synuclein pathology in a Parkinson\u2019s disease mouse model. Npj Parkinsons Dis. 12, 49 (2026).","journal-title":"Npj Parkinsons Dis."},{"key":"1479_CR36","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/s41531-025-00962-9","volume":"11","author":"X Ma","year":"2025","unstructured":"Ma, X. et al. Parkinson\u2019s disease with possible REM sleep behavior disorder correlated with more severe glymphatic system dysfunction. Npj Parkinsons Dis. 11, 82 (2025).","journal-title":"Npj Parkinsons Dis."},{"key":"1479_CR37","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.molmed.2024.04.010","volume":"30","author":"L Goodman","year":"2024","unstructured":"Goodman, L., Moulton, M., Lin, G. & Bellen, H. Does glial lipid dysregulation alter sleep in Alzheimer\u2019s \u2018s and Parkinson\u2019s \u2018 s disease?. Trends Mol. Med. 30, 913\u2013923 (2024).","journal-title":"Trends Mol. Med."},{"key":"1479_CR38","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nrneurol.2017.188","volume":"14","author":"M Sweeney","year":"2018","unstructured":"Sweeney, M., Sagare, A. & Zlokovic, B. Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat. Rev. Neurol. 14, 133\u2013150 (2018).","journal-title":"Nat. Rev. Neurol."},{"key":"1479_CR39","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/mds.26424","volume":"30","author":"R Postuma","year":"2015","unstructured":"Postuma, R. et al. MDS clinical diagnostic criteria for Parkinson\u2019s disease. Mov. Disord. 30, 1591\u20131599 (2015).","journal-title":"Mov. Disord."},{"key":"1479_CR40","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1002\/mds.29005","volume":"37","author":"G Wenning","year":"2022","unstructured":"Wenning, G. et al. The movement disorder society criteria for the diagnosis of multiple system atrophy. Mov. Disord. 37, 1131\u20131148 (2022).","journal-title":"Mov. Disord."},{"key":"1479_CR41","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1212\/WNL.0b013e3181fc29c9","volume":"75","author":"J Dalrymple-Alford","year":"2010","unstructured":"Dalrymple-Alford, J. et al. The MoCA Well-suited screen for cognitive impairment in Parkinson disease. Neurology. 75, 1717\u20131725 (2010).","journal-title":"Neurology."},{"key":"1479_CR42","doi-asserted-by":"publisher","first-page":"e70082","DOI":"10.1111\/cns.70082","volume":"30","author":"X Liu","year":"2024","unstructured":"Liu, X. et al. Exploratory analysis of the association between plasma ceramide alterations and cognitive dysfunction in Parkinson\u2019s disease. Cns Neurosci. Ther. 30, e70082 (2024).","journal-title":"Cns Neurosci. Ther."},{"key":"1479_CR43","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05699-2","volume":"22","author":"Q Lai","year":"2024","unstructured":"Lai, Q., Wang, N., Wang, B. & Chen, Y. The correlation of GluR3B antibody with T lymphocyte subsets and inflammatory factors and their role in the progression of epilepsy. J. Transl. Med. 22, 877 (2024).","journal-title":"J. Transl. Med."},{"key":"1479_CR44","doi-asserted-by":"publisher","first-page":"e70745","DOI":"10.1002\/alz.70745","volume":"21","author":"W Kwapong","year":"2025","unstructured":"Kwapong, W. et al. Retinal microvascular alterations in Alzheimer\u2019s disease: linking blood plasma biomarkers and cerebral small vessel pathology. Alzheimers Dement. 21, e70745 (2025).","journal-title":"Alzheimers Dement."}],"container-title":["npj Parkinson's Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41531-026-01479-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-026-01479-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-026-01479-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:02:55Z","timestamp":1792699375000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41531-026-01479-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,16]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1479"],"URL":"https:\/\/doi.org\/10.1038\/s41531-026-01479-5","relation":{},"ISSN":["2373-8057"],"issn-type":[{"value":"2373-8057","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,16]]},"assertion":[{"value":"29 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"258"}}