{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:48:40Z","timestamp":1790844520187,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010146","name":"Alzheimer Forschung Initiative","doi-asserted-by":"publisher","award":["17022"],"award-info":[{"award-number":["17022"]}],"id":[{"id":"10.13039\/100010146","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010146","name":"Alzheimer Forschung Initiative","doi-asserted-by":"publisher","award":["20026"],"award-info":[{"award-number":["20026"]}],"id":[{"id":"10.13039\/100010146","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The hallmark of various neurodegenerative diseases is the accumulation and aggregation of amyloidogenic proteins, such as amyloid\u2010beta (A\u03b2) and tau in Alzheimer's disease (\n                    <jats:sc>AD<\/jats:sc>\n                    ) and alpha\u2010synuclein (aSyn) in synucleinopathies. Many neurodegenerative diseases express mixed pathology. For instance, Lewy bodies are reported in tauopathies and neurofibrillary tau\u2010tangles are detected in synucleinopathies, suggesting a potential co\u2010existence or crosstalk of misfolded aSyn and tau. In the present study, we investigated the binding characteristics of monomeric aSyn with different tau isoforms by using surface plasmon resonance (SPR) spectroscopy allowing monitoring direct protein\u2013protein interactions and their potential co\u2010localization using SH\u2010SY5Y cells. The calculation of the binding parameters (association and dissociation rate constants) indicated the strongest binding affinity between aSyn and tau isoform 1N3R followed by tau 2N3R and tau 2N4R. Co\u2010localization studies in SH\u2010SY5Y cells, treated with aSyn and all six tau isoforms revealed an intracellular co\u2010localization of aSyn with different isoforms of tau. Subcellular fractionation confirmed the cellular uptake and colocalization of tau and aSyn in the same compartment, showing their expression in membrane, nuclear, and cytoskeletal fractions. Understanding the intricate interplay between aSyn and tau is crucial for unraveling the pathophysiology of PD,\n                    <jats:sc>AD<\/jats:sc>\n                    , and related neurodegenerative disorders, ultimately paving the way for the development of effective treatments targeting this interaction. In conclusion, our data indicate that aSyn and tau are direct interaction partners with varying binding affinities depending on the tau isoform. This interaction may be significant for understanding the pathophysiology of dementia with mixed pathologies.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70053-fig-0004-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70053","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:03:04Z","timestamp":1743552184000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Alpha\u2010Synuclein Demonstrates Varying Binding Affinities With Different Tau Isoforms"],"prefix":"10.1111","volume":"169","author":[{"given":"Anna\u2010Lisa","family":"Fischer","sequence":"first","affiliation":[{"name":"Department of Neurology University Medical Center G\u00f6ttingen and the German Center for Neurodegenerative Diseases (DZNE)  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center G\u00f6ttingen and the German Center for Neurodegenerative Diseases (DZNE)  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Thom","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center G\u00f6ttingen and the German Center for Neurodegenerative Diseases (DZNE)  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saima","family":"Zafar","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center G\u00f6ttingen and the German Center for Neurodegenerative Diseases (DZNE)  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelam","family":"Younas","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center G\u00f6ttingen and the German Center for Neurodegenerative Diseases (DZNE)  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"da Silva Correia","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center G\u00f6ttingen and the German Center for Neurodegenerative Diseases (DZNE)  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"da Silva Correia","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center G\u00f6ttingen and the German Center for Neurodegenerative Diseases (DZNE)  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sezgi Canaslan","family":"Eyyuboglu","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center G\u00f6ttingen and the German Center for Neurodegenerative Diseases (DZNE)  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Zerr","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center G\u00f6ttingen and the German Center for Neurodegenerative Diseases (DZNE)  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102981200"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2004-6412"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)03082-1"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01848-X"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050002"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90590-H"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2020.09.030"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0490-10.2010"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2012.06.015"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04857.x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4644(20000801)78:2<305::AID-JCB12>3.0.CO;2-W"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.9b00215"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006212"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22321"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.01.014"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2010.05.004"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-008-0383-1"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2000.7527"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20819"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1082324"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03641.x"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(89)90210-9"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208194200"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07116.x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0508-2"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.057"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2000.tb00269.x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.01.043"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30291-5"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-002-0644-3"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/62.4.389"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.06.036"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-008-0347-5"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.36.25481"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410220411"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(89)90077-9"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000165987.89198.65"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2012.03.019"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107045200"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2004.01.007"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e3282f03db4"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199903)45:3<353::AID-ANA11>3.0.CO;2-4"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20387"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-08-02804.1988"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010100443"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-9-43"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3043"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13109"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4914(03)00007-8"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0317167100047405"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02160-8"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu011"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050454"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000271090.28148.24"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309127200"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.487"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.09.011"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/42166"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9490"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-005-0022-z"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21145030"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.06.3053"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0297-11.2011"},{"key":"e_1_2_11_65_1","first-page":"S40","article-title":"Parkinson's Disease\u2010Part 1: Pathophysiology, Symptoms, Burden, Diagnosis, and Assessment","volume":"14","author":"Weintraub D.","year":"2008","journal-title":"American Journal of Managed Care"},{"key":"e_1_2_11_66_1","first-page":"S49","article-title":"Parkinson's Disease\u2010Part 2: Treatment of Motor Symptoms","volume":"14","author":"Weintraub D.","year":"2008","journal-title":"American Journal of Managed Care"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.3.398"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2010.06.017"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/64.3.245"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405456200"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.70053","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T03:53:05Z","timestamp":1748231585000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.70053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":69,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/jnc.70053"],"URL":"https:\/\/doi.org\/10.1111\/jnc.70053","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/JNC.70053\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.70053\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.70053\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.70053\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.70053\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.70053\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.70053\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2024-08-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70053"}}