Single-Cell Multi-Modal Differential Analysis of the Human Neo-Cortex in HIV Infection Reveals Similarities with Hallmarks of Alzheimer’s Disease

Single-Cell Multi-Modal Differential Analysis of the Human Neo-Cortex in HIV Infection Reveals Similarities with Hallmarks of Alzheimer’s Disease | 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 Biological Sciences - Article Single-Cell Multi-Modal Differential Analysis of the Human Neo-Cortex in HIV Infection Reveals Similarities with Hallmarks of Alzheimer’s Disease Arpita Joshi, Pietro Paolo sanna This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7636879/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Cognitive impairment in people with HIV (PWH) remains prevalent despite viral suppression. To provide insights into the cellular mechanisms of pathogenesis, we carried out a multi-modal pan cell-type specific differential analysis of the frontal cortex of PWH. We show cell type-specific dysregulations of oxidative phosphorylation, glycolysis, ribosomes and translation, DNA damage, and neuroinflammation in PWH. Key genes and pathways identified showed a considerable overlap with transcriptional hallmarks of Alzheimer’s disease (AD) and involved AD vulnerable cell types, among others. We computed several differentially accessible chromatin sites in all major cell-types. Neuronal genes with perturbed chromatin accessibility regions were enriched in synaptic signaling genes supporting an epigenetic contribution to cognitive impairment in HIV. Convergent mechanisms of pathogenesis between HIV and AD support that broad therapeutic targets can be identified to ameliorate neurodegeneration and neuroinflammation in HIV and neurodegenerative conditions such as AD. Health sciences/Diseases/Neurological disorders/Neurodegeneration Biological sciences/Neuroscience/Computational neuroscience Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryFigure3.pdf Supplementary Figure 3 SupplementaryFigure1.pdf Supplementary Figure 1 SupplementaryFigure2.pdf Supplementary Figure 2 SupplementaryTable1.xlsx Supplementary Table 1 SupplementaryTable6.xlsx Supplementary Table 6 SupplementaryTable2.xlsx Supplementary Table 2 SupplementaryTable4.xlsx Supplementary Table 4 SupplementaryTable3.xlsx Supplementary Table 3 SupplementaryTable5.xlsx Supplementary Table 5 Cite Share Download PDF Status: Under Review 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. 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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-7636879","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":527391139,"identity":"87e80303-41fc-4f34-9d81-9b3e5de0bd2c","order_by":0,"name":"Arpita 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