Truncated tau modulates neuron-glia signaling through CX3CL1-CX3CR1 and CD47-SIRP-α pathways.

Truncated tau modulates neuron-glia signaling through CX3CL1-CX3CR1 and CD47-SIRP-α pathways. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Truncated tau modulates neuron-glia signaling through CX3CL1-CX3CR1 and CD47-SIRP-α pathways. Petra Majerova, Monika Zilkova, Katarina Bhide, Andrej Kovac This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4868529/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Tauopathies encompass a group of disorders characterized by abnormal accumulation of tau protein into neurofibbrilary pathology and neuroinflammation. Understanding how glial cells interact with neurons is important to unraveling the complex mechanisms driving the progression of tauopathies. In this study, we established a multi-component cellular model for tauopathies comprising neuronal cells inducible expressing pathological truncated tau, primary microglia, and astrocytes. We successfully identified optimal culture conditions, with 1% serum supplemented with B27 proving to be most effective in enhancing neuronal protein expression, tau levels, and cell viability. This condition supported improved neuronal differentiation and synaptic marker expression, reflecting a more robust neuronal phenotype compared to monocultures. The increase in pro-inflammatory cytokines production underscores the model's capability to replicate the inflammatory environment characteristic of neurodegenerative diseases. Importantly, we observed that truncated tau significantly modulates key signalling pathways, notably the CX3CL1-CX3CR1 and CD47-SIRP-α pathways. We found that pathological changes in tauopathies altered neuron-glia interactions, leading them towards a more quiescent glial state.The alterations in signaling were accompanied by changes in tau phosphorylation, with neuroinflammation exacerbating hyperphosphorylation of truncated tau, while minimally affecting endogenous tau. In conclusion, our study highlights that pathological truncated tau significantly affects the expression of membrane-anchored fractalkine. This differential modulation, coupled with changes in inflammatory conditions, suggests that early-stage tau pathology can influence neuroinflammatory responses and may still allow neuronal cells to engage in protective mechanisms. Tauopathies inflammation glial cells fractalkine SIRP-CD47 Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4868529","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":342165898,"identity":"0ef44f64-6f56-434d-ac42-1a4344fe022f","order_by":0,"name":"Petra Majerova","email":"","orcid":"","institution":"Institute of Neuroimmunology","correspondingAuthor":false,"prefix":"","firstName":"Petra","middleName":"","lastName":"Majerova","suffix":""},{"id":342165899,"identity":"c88b036d-d66f-4a4a-bdac-d18c2574d6a2","order_by":1,"name":"Monika Zilkova","email":"","orcid":"","institution":"Institute of Neuroimmunology","correspondingAuthor":false,"prefix":"","firstName":"Monika","middleName":"","lastName":"Zilkova","suffix":""},{"id":342165900,"identity":"51e87706-b3ca-4819-b8d1-63e959ba6780","order_by":2,"name":"Katarina Bhide","email":"","orcid":"","institution":"University of Veterinary Medicine in Košice","correspondingAuthor":false,"prefix":"","firstName":"Katarina","middleName":"","lastName":"Bhide","suffix":""},{"id":342165901,"identity":"f4e8e786-6c10-459a-9970-f79618e08e01","order_by":3,"name":"Andrej Kovac","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYHACAwYGHhABBB8gXAbGBmK1MM4gXguUYOYhRgv/7OZtHz7IMBjzSyQ//Gzzxy5xO/sB5o8z8GiRuHOseOYMHgYzyRlpxtK5bcmJO3sS2CQ34HPWjRxjZh4eBhuDMwfMmHMbmI0NDiSwMT7Ao0MepOUPWMvxb8wWf+qNDc4/YP6IT4sBSAswxMwMjveYMTOwHZYzuJHAgNdhhjfSihl7eCSMJdt7iiV7247LWc542CaJz/tyN5I3M/zssTHsZ2bf+OHHn2oec/7kwx978HkfBBh7JFC4DYQ0AMEPItSMglEwCkbByAUAPyVJjWy8hoAAAAAASUVORK5CYII=","orcid":"","institution":"Institute of Neuroimmunology","correspondingAuthor":true,"prefix":"","firstName":"Andrej","middleName":"","lastName":"Kovac","suffix":""}],"badges":[],"createdAt":"2024-08-06 12:38:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4868529/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4868529/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":70010689,"identity":"f0682604-aed5-4baf-a407-d58c9f2d2a6c","added_by":"auto","created_at":"2024-11-27 13:02:57","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1289643,"visible":true,"origin":"","legend":"","description":"","filename":"Majerovaetal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4868529/v1_covered_d5d9a6d4-be6a-430c-b57a-8531e823dc30.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Truncated tau modulates neuron-glia signaling through CX3CL1-CX3CR1 and CD47-SIRP-α pathways.","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Tauopathies, inflammation, glial cells, fractalkine, SIRP-CD47","lastPublishedDoi":"10.21203/rs.3.rs-4868529/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4868529/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eTauopathies encompass a group of disorders characterized by abnormal accumulation of tau protein into neurofibbrilary pathology and neuroinflammation. Understanding how glial cells interact with neurons is important to unraveling the complex mechanisms driving the progression of tauopathies. In this study, we established a multi-component cellular model for tauopathies comprising neuronal cells inducible expressing pathological truncated tau, primary microglia, and astrocytes. We successfully identified optimal culture conditions, with 1% serum supplemented with B27 proving to be most effective in enhancing neuronal protein expression, tau levels, and cell viability. This condition supported improved neuronal differentiation and synaptic marker expression, reflecting a more robust neuronal phenotype compared to monocultures. The increase in pro-inflammatory cytokines production underscores the model's capability to replicate the inflammatory environment characteristic of neurodegenerative diseases. 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