{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:29:12Z","timestamp":1793392152149,"version":"4.5.0"},"reference-count":43,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"<jats:sec id=\"ab-noi230049-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Knowledge is lacking on the prevalence and prognosis of individuals with a \u03b2-amyloid\u2013negative, tau-positive (A\u2212T+) cerebrospinal fluid (CSF) biomarker profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi230049-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To estimate the prevalence of a CSF A\u2212T+ biomarker profile and investigate its clinical implications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi230049-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This was a retrospective cohort study of the cross-sectional multicenter University of Gothenburg (UGOT) cohort (November 2019-January 2021), the longitudinal multicenter Alzheimer Disease Neuroimaging Initiative (ADNI) cohort (individuals with mild cognitive impairment [MCI] and no cognitive impairment; September 2005-May 2022), and 2 Wisconsin cohorts, Wisconsin Alzheimer Disease Research Center and Wisconsin Registry for Alzheimer Prevention (WISC; individuals without cognitive impairment; February 2007-November 2020). This was a multicenter study, with data collected from referral centers in clinical routine (UGOT) and research settings (ADNI and WISC). Eligible individuals had 1 lumbar puncture (all cohorts), 2 or more cognitive assessments (ADNI and WISC), and imaging (ADNI only) performed on 2 separate occasions. Data were analyzed on August 2022 to April 2023.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi230049-7\">\n                    <jats:title>Exposures<\/jats:title>\n                    <jats:p>\n                      Baseline CSF A\u03b242\/40 and phosphorylated tau (p-tau)181; cognitive tests (ADNI: modified preclinical Alzheimer cognitive composite [mPACC]; WISC: modified 3-test PACC [PACC-3]). Exposures in the ADNI cohort included [\n                      <jats:sup>18<\/jats:sup>\n                      F]-florbetapir amyloid positron emission tomography (PET), magnetic resonance imaging (MRI), [\n                      <jats:sup>18<\/jats:sup>\n                      F]-fluorodeoxyglucose PET (FDG-PET), and cross-sectional tau-PET (ADNI: [\n                      <jats:sup>18<\/jats:sup>\n                      F]-flortaucipir, WISC: [\n                      <jats:sup>18<\/jats:sup>\n                      F]-MK6240).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi230049-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Primary outcomes were the prevalence of CSF AT biomarker profiles and continuous longitudinal global cognitive outcome and imaging biomarker trajectories in A\u2212T+ vs A\u2212T\u2212 groups. Secondary outcomes included cross-sectional tau-PET.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi230049-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 7679 individuals (mean [SD] age, 71.0 [8.4] years; 4101 male [53%]) were included in the UGOT cohort, 970 individuals (mean [SD] age, 73 [7.0] years; 526 male [54%]) were included in the ADNI cohort, and 519 individuals (mean [SD] age, 60 [7.3] years; 346 female [67%]) were included in the WISC cohort. The prevalence of an A\u2212T+ profile in the UGOT cohort was 4.1% (95% CI, 3.7%-4.6%), being less common than the other patterns. Longitudinally, no significant differences in rates of worsening were observed between A\u2212T+ and A\u2212T\u2212 profiles for cognition or imaging biomarkers. Cross-sectionally, A\u2212T+ had similar tau-PET uptake to individuals with an A\u2212T\u2212 biomarker profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi230049-10\">\n                    <jats:title>Conclusion and Relevance<\/jats:title>\n                    <jats:p>Results suggest that the CSF A\u2212T+ biomarker profile was found in\u2009approximately\u20095% of lumbar punctures and was not associated with a higher rate of cognitive decline or biomarker signs of disease progression compared with biomarker-negative individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaneurol.2023.2338","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T11:34:34Z","timestamp":1690803274000},"page":"969","source":"Crossref","is-referenced-by-count":48,"title":["Prevalence and Clinical Implications of a \u03b2-Amyloid\u2013Negative, Tau-Positive Cerebrospinal Fluid Biomarker Profile in Alzheimer Disease"],"prefix":"10.1001","volume":"80","author":[{"given":"Pontus","family":"Erickson","sequence":"first","affiliation":[{"name":"Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Simr\u00e9n","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wagner S.","family":"Brum","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilda E.","family":"Ennis","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Wisconsin-Madison, Madison"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendlyn","family":"Kollmorgen","sequence":"additional","affiliation":[{"name":"Roche Diagnostics GmbH, Penzberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivonne","family":"Suridjan","sequence":"additional","affiliation":[{"name":"Roche Diagnostics GmbH, Penzberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Langhough","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Wisconsin-Madison, Madison"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin M.","family":"Jonaitis","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Wisconsin-Madison, Madison"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Van Hulle","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Wisconsin-Madison, Madison"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobey J.","family":"Betthauser","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Wisconsin-Madison, Madison"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia M.","family":"Carlsson","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Wisconsin-Madison, Madison"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison"},{"name":"Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison"},{"name":"Geriatric Research Education and Clinical Center of the Wm. 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