{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T07:40:27Z","timestamp":1792309227195,"version":"4.4.0"},"reference-count":73,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The causes of late onset Alzheimer disease (LOAD) are not known but several recent lines of evidence implicate the adaptive immune system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To characterize the adaptive immune system among Midwestern Amish participating in longitudinal studies of aging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We immunosequenced the T\u2010cell receptor (TCR) beta chain from genomic DNA of 72 participants, including those with clinically diagnosed LOAD (\n                      <jats:italic>n<\/jats:italic>\n                      = 6), mild cognitive impairment (MCI;\n                      <jats:italic>n<\/jats:italic>\n                      = 16), cognitive impairment but not AD (\n                      <jats:italic>n<\/jats:italic>\n                      = 3), and 35 cognitively unaffected. For a subset of participants, LOAD pathogenesis plasma biomarkers were available.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TCR sequence diversity measured as Simpson's clonality was lower among LOAD+MCI compared with non\u2010LOAD, but these differences were not independent of age. Relatively few clonotypes (exact nucleotide sequences) were shared across participants; of those few shared include the Epstein Barr virus associated clonotype. HLA\u2010A*03:01 and several HLA\u2010DRB1 alleles were under\u2010represented among LOAD+MCI participants compared with cognitively unaffected participants, but these associations were no longer significant in adjusted analyses. Among LOAD+MCI participants, increased p\u2010tau181 was nominally associated with decreased TCR sequence diversity, and the nominal association was independent of age; however, this association did not remain statistically significant after strict correction for multiple testing and the limited sample size precluded formal tests of heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this limited Midwestern Amish sample, the preliminary TCR diversity trends are consistent with the involvement of the adaptive immune system in LOAD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ahg.70063","type":"journal-article","created":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T07:10:36Z","timestamp":1792307436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evidence for Reduced Somatic T\u2010Cell Receptor Sequence Diversity Profiles Among Midwestern Amish in an Aging Cohort Study"],"prefix":"10.1111","author":[{"given":"Lauren A.","family":"Cruz","sequence":"first","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristy L.","family":"Miskimen","sequence":"additional","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica N.","family":"Cooke Bailey","sequence":"additional","affiliation":[{"name":"East Carolina University  Greenville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Kinzy","sequence":"additional","affiliation":[{"name":"East Carolina University  Greenville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeunjoo E.","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee A.","family":"Laux","sequence":"additional","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penelope","family":"Miron","sequence":"additional","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula K.","family":"Ogrocki","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospitals Cleveland Medical Center  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan J.","family":"Lerner","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospitals Cleveland Medical Center  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Lynn","sequence":"additional","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarada L.","family":"Fuzzell","sequence":"additional","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherri D.","family":"Hochstetler","sequence":"additional","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Konidari","sequence":"additional","affiliation":[{"name":"The Dr. John T. 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