Gene Expression Profile of Synchronized Cells Identifies Alzheimer's Disease in Autopsy Validated Skin and Blood Samples 

Gene Expression Profile of Synchronized Cells Identifies Alzheimer's Disease in Autopsy Validated Skin and Blood Samples | 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 Article Gene Expression Profile of Synchronized Cells Identifies Alzheimer's Disease in Autopsy Validated Skin and Blood Samples Florin V. Chirila, William MacTurk, Jack Wallace, Guang Xu, Daniel L. Alkon This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5270779/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 A gene expression profile has not been identified for late-onset Alzheimer's Disease (LOAD) in more than 95% of cases. However, autosomal dominant genes are known for early-onset (EOAD). Moreover, the genetic convergences between familial EOAD and sporadic LOAD have not previously been identified despite the common neuropathology. Here, synchronized skin fibroblast samples from individuals with LOAD, confirmed by autopsy, revealed 36 statistically significant (P < 0.05) LOAD-dysregulated genes, with 26 showing an essential gap with non-Alzheimer's disease (non-ADD) dementia patients. Notably, five LOAD-dysregulated genes in the skin - FAM149B, NHLH1, SHISA5, URB2, and WASF2 - were also dysregulated in blood B-lymphocytes. Importantly, an additional 18 LOAD-dysregulated gene families in the skin were validated in the blood. In total, 23 LOAD-dysregulated gene families in the skin were confirmed in the blood. An intriguing and novel aspect is the genetic convergence between late-onset and early-onset Alzheimer's disease, demonstrated by dysregulated gene families ADAM, IL, and RAB. The gene expression profile aligns remarkably well with prior autopsy-validated biomarkers: Morphometric Imaging, PKC epsilon, Cell Size, Growth Rate, and Protein Amount. Our findings indicate a promising potential for personalized genomic profiling in LOAD diagnosis and treatment, offering hope for more effective and targeted approaches. Health sciences/Diseases Health sciences/Diseases/Neurological disorders Health sciences/Diseases/Neurological disorders/Neurodegenerative diseases Health sciences/Diseases/Neurological disorders/Neurodegenerative diseases/Alzheimers disease Full Text Additional Declarations Competing interest reported. FVC and DLA own shares of Synaps Dx. FVC owns Spot DX All other authors declare they have no competing interests 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5270779","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":376961828,"identity":"8295afec-7c1a-4933-800e-b02fd376c4c6","order_by":0,"name":"Florin V. 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