{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:24:56Z","timestamp":1784309096454,"version":"3.55.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100016948","name":"Tau Consortium","doi-asserted-by":"publisher","award":["R01 AG071858"],"award-info":[{"award-number":["R01 AG071858"]}],"id":[{"id":"10.13039\/100016948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurodegeneration"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Clinical studies have long observed that neurodegenerative disorders display a range of symptoms and pathological features and, in some cases, overlap, suggesting that these diseases exist on a spectrum. Dementia with Lewy Bodies (DLB), a synucleinopathy, is a prominent example, where symptomatic similarities with tauopathy, Alzheimer\u2019s disease, are observed. Although tau pathology has been observed in DLB, the interplay between tau and \u03b1-synuclein is poorly understood at a molecular level.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Quantitative mass spectrometry analysis was used to measure protein abundance in the insoluble fraction from cortical brain tissue from pathologically diagnosed DLB subjects (<jats:italic>n<\/jats:italic>\u2009=\u200930) and age-matched controls (<jats:italic>n<\/jats:italic>\u2009=\u200929). Using tau abundance, we stratified the DLB subjects into two subgroups termed DLBTau<jats:sup>+<\/jats:sup> (higher abundance) and DLBTau<jats:sup>\u2212<\/jats:sup> (lower abundance). We conducted proteomic analysis to characterize and compare the cortical proteome of DLB subjects exhibiting elevated tau, as well as the molecular modifications of tau and \u03b1-synuclein to explore the dynamic between tau and \u03b1-synuclein pathology in these patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Proteomic analyses revealed distinct global protein dysregulations in DLBTau<jats:sup>+<\/jats:sup> and DLBTau<jats:sup>\u2212<\/jats:sup> subjects when compared to controls. Notably, DLBTau<jats:sup>+<\/jats:sup> patients exhibited increased levels of tau, along with ubiquitin, and APOE, indicative of cortical proteome alterations associated with elevated tau. Comparing DLBTau<jats:sup>+<\/jats:sup> and DLBTau<jats:sup>\u2212<\/jats:sup> groups, we observed significant upregulation of cytokine signaling and metabolic pathways in DLBTau<jats:sup>\u2212<\/jats:sup> patients, while DLBTau<jats:sup>+<\/jats:sup> subjects showed increases in protein ubiquitination processes and regulation of vesicle-mediated transport. Additionally, we examined the post-translational modification patterns of tau and \u03b1-synuclein. Our analysis revealed distinct phosphorylation and ubiquitination sites on \u03b1-synuclein between groups. Moreover, we observed increased modifications on tau specifically within the DLBTau<jats:sup>+<\/jats:sup> subgroup.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This molecular-level data supports the idea of neurodegenerative disease as a continuum of diseases with distinct PTM profiles DLBTau<jats:sup>+<\/jats:sup> and DLBTau<jats:sup>\u2212<\/jats:sup> patients in comparison to AD. These findings further emphasize the importance of identifying specific and tailored therapeutic approaches targeting the involved proteopathies in the neurodegenerative disease spectrum.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13024-024-00782-0","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:21:19Z","timestamp":1734567679000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Dementia with lewy bodies patients with high tau levels display unique proteome profiles"],"prefix":"10.1186","volume":"19","author":[{"given":"Sinead","family":"Greally","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukesh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schlaffner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"van der Heijden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth S.","family":"Lawton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deeptarup","family":"Biswas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Berretta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanno","family":"Steen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith A.","family":"Steen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"issue":"10","key":"782_CR1","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1002\/mds.20527","volume":"20","author":"D Aarsland","year":"2005","unstructured":"Aarsland D, Zaccai J, Brayne C. A systematic review of prevalence studies of dementia in Parkinson\u2019s disease. Mov Disord. 2005;20(10):1255\u201363.","journal-title":"Mov Disord"},{"key":"782_CR2","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.jocn.2020.04.088","volume":"78","author":"S Das","year":"2020","unstructured":"Das S, Zhang Z, Ang LC. Clinicopathological overlap of neurodegenerative diseases: A comprehensive review. J Clin Neurosci. 2020;78:30\u20133.","journal-title":"J Clin Neurosci"},{"issue":"1","key":"782_CR3","first-page":"89","volume":"17","author":"JP Brion","year":"1985","unstructured":"Brion JP, et al. Neurofibrillary tangles of Alzheimer\u2019s disease: an immunohistochemical study. J Submicrosc Cytol. 1985;17(1):89\u201396.","journal-title":"J Submicrosc Cytol"},{"issue":"4","key":"782_CR4","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1097\/00005072-199804000-00005","volume":"57","author":"MC Irizarry","year":"1998","unstructured":"Irizarry MC, et al. Nigral and cortical Lewy bodies and dystrophic nigral neurites in Parkinson\u2019s disease and cortical Lewy body disease contain alpha-synuclein immunoreactivity. J Neuropathol Exp Neurol. 1998;57(4):334\u20137.","journal-title":"J Neuropathol Exp Neurol"},{"key":"782_CR5","doi-asserted-by":"crossref","unstructured":"Foguem C, Manckoundia P. Lewy Body Disease: Clinical and Pathological \"Overlap Syndrome\" Between Synucleinopathies (Parkinson Disease) and Tauopathies (Alzheimer Disease). Curr Neurol Neurosci Rep. 2018;18(5):24.","DOI":"10.1007\/s11910-018-0835-5"},{"issue":"4","key":"782_CR6","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1093\/jnen\/62.4.389","volume":"62","author":"T Ishizawa","year":"2003","unstructured":"Ishizawa T, et al. Colocalization of Tau and Alpha-Synuclein Epitopes in Lewy Bodies. 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Pharmacol Ther. 2013;138(3):311\u201322.","journal-title":"Pharmacol Ther"}],"container-title":["Molecular Neurodegeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13024-024-00782-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13024-024-00782-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13024-024-00782-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T01:03:08Z","timestamp":1734570188000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecularneurodegeneration.biomedcentral.com\/articles\/10.1186\/s13024-024-00782-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,19]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["782"],"URL":"https:\/\/doi.org\/10.1186\/s13024-024-00782-0","relation":{},"ISSN":["1750-1326"],"issn-type":[{"value":"1750-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,19]]},"assertion":[{"value":"1 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study involved the use of brain tissue specimens from cohorts of patients with DLB and aged controls from the NeuroBiobank at the McLean hospital and Harvard. All participants and families gave their written and informed consent for the utilization of their biomaterials for scientific research.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Nothing to declare.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"98"}}