{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:36:10Z","timestamp":1790807770802,"version":"4.1.0"},"posted":{"date-parts":[[2023,9,27]]},"group-title":"Neuroscience","reference-count":33,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,1,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>INTRODUCTION<\/jats:title>\n                  <jats:p>Altered immune signatures are emerging as a central theme in neurodegenerative disease, yet little is known about immune responses in early-onset Alzheimer\u2019s disease (EOAD).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>We examined single-cell RNA-sequencing (scRNA-seq) data from peripheral blood mononuclear cells (PBMCs) and droplet digital (dd)PCR data from CD4 T cells from participants with EOAD and clinically normal controls.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>\n                    We analyzed ~182,000 PBMCs by scRNA-seq and discovered increased interferon signaling-associated gene (ISAG) expression and striking expansion of antiviral-like ISAG\n                    <jats:sup>hi<\/jats:sup>\n                    T cells in EOAD. We isolated CD4 T cells from additional EOAD cases and confirmed increased expression of ISAG\n                    <jats:sup>hi<\/jats:sup>\n                    marker genes. Publicly available cerebrospinal fluid leukocyte scRNA-seq data from late-onset mild cognitive impairment and AD also revealed increased expression of interferon-response genes.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>\n                    ISAG\n                    <jats:sup>hi<\/jats:sup>\n                    T cells, apparently primed for antiviral activity, are expanded in EOAD. Additional research into these cells and the role of heightened peripheral IFN signaling in neurodegeneration is warranted.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.09.26.559634","type":"posted-content","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T21:10:28Z","timestamp":1695849028000},"source":"Crossref","is-referenced-by-count":2,"title":["Expansion of highly interferon-responsive T cells in early-onset Alzheimer\u2019s disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3440-8859","authenticated-orcid":false,"given":"Daniel W.","family":"Sirkis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7049-6281","authenticated-orcid":false,"given":"Caroline Warly","family":"Solsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor 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