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Recent evidence suggests the involvement of peripheral immune cells in the disease, but the underlying mechanisms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We comprehensively mapped peripheral immune changes in AD patients with mild cognitive impairment (MCI) or dementia compared to controls, using cytometry by time-of-flight (CyTOF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found an adaptive immune signature in AD, and specifically highlight the accumulation of PD1\n                      <jats:sup>+<\/jats:sup>\n                      CD57\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T effector memory cells re-expressing CD45RA in the MCI stage of AD. In addition, several innate and adaptive immune cell subsets correlated to cerebrospinal fluid (CSF) biomarkers of AD neuropathology and measures for cognitive decline. Intriguingly, subsets of memory T and B cells were negatively associated with CSF biomarkers for tau pathology, neurodegeneration and neuroinflammation in AD patients. Lastly, we established the influence of the APOE \u03b54 allele on peripheral immunity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings illustrate significant peripheral immune alterations associated with both early and late clinical stages of AD, emphasizing the necessity for further investigation into how these changes influence underlying brain pathology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13024-024-00726-8","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T12:03:02Z","timestamp":1713960182000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Adaptive immune changes associate with clinical progression of Alzheimer\u2019s disease"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7569-0470","authenticated-orcid":false,"given":"Lynn","family":"van Olst","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alwin","family":"Kamermans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sem","family":"Halters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne M. 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These participants visited the Alzheimer's Center in Amsterdam between May 2018 and March 2020 for a standardized dementia screening process which included neurological, physical, and neuropsychological assessments, and brain MRI. An option for a lumbar puncture was also presented. Diagnoses of MCI and dementia were made in alignment with the NIA-AA criteria during a multidisciplinary consensus meeting, as per the guidelines applicable at the time. The study was endorsed by the Medical Ethics Committee of the VU University Medical Center and adhered to the principles of the Helsinki Declaration of 1975. Participants gave their written informed consent for the utilization of their medical data and biomaterials for scientific research.Furthermore, an independent neuropathological cohort was employed to examine CD8<sup>+<\/sup> T and CD57<sup>+<\/sup> CD8<sup>+<\/sup> T cells in the middle temporal gyrus of AD patients with pathologically confirmed amyloid pathology. Autopsies were conducted with permission, and tissues were used alongside access to medical records for research purposes in accordance with the relevant ethical approvals (project number 1423). The Netherlands Brain Bank's informed consent forms were approved by the Medical Ethics Committee of the VU Medical Center in Amsterdam (2009\/148).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"CET has research contracts with Acumen, ADx Neurosciences, AC-Immune, Alamar, Aribio, Axon Neurosciences, Beckman-Coulter, BioConnect, Bioorchestra, Brainstorm Therapeutics, Celgene, Cognition Therapeutics, EIP Pharma, Eisai, Eli Lilly, Fujirebio, Instant Nano Biosensors, Novo Nordisk, Olink, PeopleBio, Quanterix, Roche, Toyama, Vivoryon. CET\u00a0is editor in chief of Alzheimer Research and Therapy, and serves on editorial boards of Medidact Neurologie\/Springer, and Neurology: Neuroimmunology & Neuroinflammation. CET\u00a0had consultancy\/speaker contracts for Eli Lilly, Merck, Novo Nordisk, Olink and Roche.\u00a0WMF has performed contract research for Biogen MA Inc, and Boehringer Ingelheim. WMF has been an invited speaker at Boehringer Ingelheim, Biogen MA Inc, Danone, Eisai, WebMD Neurology (Medscape), and Springer Healthcare. WMF has been a consultant to Oxford Health Policy Forum CIC, Roche, and Biogen MA Inc. WMF participated in advisory boards of Biogen MA Inc and Roche. WMF was associate editor of Alzheimer, Research & Therapy in 2020\/2021. WMF is associate editor at Brain.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"38"}}