{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:33:22Z","timestamp":1793158402598,"version":"4.5.0"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The adaptive immune system and neurodegenerative Alzheimer's disease (AD) are intertwined in multiple ways. Recent studies have reported alterations of the adaptive immune system in early AD stages, such as preclinical AD and mild cognitive impairment (MCI) due to AD. However, the identity of specific antigenic targets and whether the respective response is beneficial or detrimental during disease progression are still open questions.<\/jats:p>\n                  <jats:p>Herein, we describe cross-sectional analyses of blood and CSF from three different study populations covering early AD stages. We employed high-dimensional mass cytometry, single-cell RNA-sequencing, ex vivo T-cell secretome analysis, and antigen presentation assays to achieve a comprehensive characterization of adaptive immune cell populations.<\/jats:p>\n                  <jats:p>Our results show that subjects at the stage of asymptomatic, preclinical AD can mount a CD4+ T helper cell response towards amyloid-\u03b2 peptide and display an early enrichment of CD8+ T effector memory cells re-expressing CD45RA (TEMRA cells) in CSF, combined with a less immunosuppressive gene signature of peripheral regulatory T cells. Conversely, in MCI we observed increased frequencies of CD8+ TEMRA\/effector cells in the periphery characterized by a pro-inflammatory gene expression profile, and generally decreased antigen responsiveness.<\/jats:p>\n                  <jats:p>Our results demonstrate the complexity of adaptive immune changes in early AD and suggest that it may be beneficial to promote specific CD4+ T-cell responses in the preclinical stage, while in MCI it may be important to therapeutically target CD8+ T-cell responses if these prove to be harmful.<\/jats:p>","DOI":"10.1093\/brain\/awaf167","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T19:59:17Z","timestamp":1746043157000},"page":"3364-3378","source":"Crossref","is-referenced-by-count":31,"title":["Altered T-cell reactivity in the early stages of Alzheimer's disease"],"prefix":"10.1093","volume":"148","author":[{"given":"Chiara","family":"Rickenbach","sequence":"first","affiliation":[{"name":"Institute for Regenerative Medicine\u2014IREM, University of Zurich , 8952 Schlieren ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Mallone","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, ETH Zurich , 8049 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"H\u00e4usle","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine\u2014IREM, University of Zurich , 8952 Schlieren ,","place":["Switzerland"]},{"name":"Institute of Microbiology, ETH Zurich , 8049 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"Frei","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine\u2014IREM, University of Zurich , 8952 Schlieren ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"Seiter","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine\u2014IREM, University of Zurich , 8952 Schlieren ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Sparano","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, University of Zurich , 8057 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tunahan","family":"Kirabali","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine\u2014IREM, University of Zurich , 8952 Schlieren ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg , S-43180 M\u00f6lndal ,","place":["Sweden"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , S-43180 M\u00f6lndal ,","place":["Sweden"]},{"name":"Paris Brain Institute, ICM, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Sorbonne University , 75013 Paris ,","place":["France"]},{"name":"Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC , 230026 Hefei ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg , S-43180 M\u00f6lndal ,","place":["Sweden"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , S-43180 M\u00f6lndal ,","place":["Sweden"]},{"name":"Department of Neurodegenerative Disease, UCL Institute of Neurology , Queen Square, London WC1N 3BG ,","place":["UK"]},{"name":"UK Dementia Research Institute at UCL , London WC1N 3BG ,","place":["UK"]},{"name":"Hong Kong Center for Neurodegenerative Diseases , Clear Water Bay, Hong Kong ,","place":["China"]},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI 53792 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Ferretti","sequence":"additional","affiliation":[{"name":"Center for Alzheimer Research, Karolinska Institute , S-17177 Stockholm 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