Prevalence and Clinical Implications of a β-Amyloid–Negative, Tau-Positive Cerebrospinal Fluid Biomarker Profile in Alzheimer Disease

Medientyp: E-Artikel
Titel: Prevalence and Clinical Implications of a β-Amyloid–Negative, Tau-Positive Cerebrospinal Fluid Biomarker Profile in Alzheimer Disease
Beteiligte: Erickson, Pontus; Simrén, Joel; Brum, Wagner S.; Ennis, Gilda E.; Kollmorgen, Gwendlyn; Suridjan, Ivonne; Langhough, Rebecca; Jonaitis, Erin M.; Van Hulle, Carol A.; Betthauser, Tobey J.; Carlsson, Cynthia M.; Asthana, Sanjay; Ashton, Nicholas J.; Johnson, Sterling C.; Shaw, Leslie M.; Blennow, Kaj; Andreasson, Ulf; Bendlin, Barbara B.; Zetterberg, Henrik; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; [...]
Erschienen: American Medical Association (AMA), 2023
Erschienen in: JAMA Neurology
Sprache: Englisch
DOI: 10.1001/jamaneurol.2023.2338
ISSN: 2168-6149
Schlagwörter: Neurology (clinical)
Entstehung:
Anmerkungen:
Beschreibung: <jats:sec id="ab-noi230049-4"><jats:title>Importance</jats:title><jats:p>Knowledge is lacking on the prevalence and prognosis of individuals with a β-amyloid–negative, tau-positive (A−T+) cerebrospinal fluid (CSF) biomarker profile.</jats:p></jats:sec><jats:sec id="ab-noi230049-5"><jats:title>Objective</jats:title><jats:p>To estimate the prevalence of a CSF A−T+ biomarker profile and investigate its clinical implications.</jats:p></jats:sec><jats:sec id="ab-noi230049-6"><jats:title>Design, Setting, and Participants</jats:title><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></jats:sec><jats:sec id="ab-noi230049-7"><jats:title>Exposures</jats:title><jats:p>Baseline CSF Aβ42/40 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 [<jats:sup>18</jats:sup>F]-florbetapir amyloid positron emission tomography (PET), magnetic resonance imaging (MRI), [<jats:sup>18</jats:sup>F]-fluorodeoxyglucose PET (FDG-PET), and cross-sectional tau-PET (ADNI: [<jats:sup>18</jats:sup>F]-flortaucipir, WISC: [<jats:sup>18</jats:sup>F]-MK6240).</jats:p></jats:sec><jats:sec id="ab-noi230049-8"><jats:title>Main Outcomes and Measures</jats:title><jats:p>Primary outcomes were the prevalence of CSF AT biomarker profiles and continuous longitudinal global cognitive outcome and imaging biomarker trajectories in A−T+ vs A−T− groups. Secondary outcomes included cross-sectional tau-PET.</jats:p></jats:sec><jats:sec id="ab-noi230049-9"><jats:title>Results</jats:title><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−T+ 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−T+ and A−T− profiles for cognition or imaging biomarkers. Cross-sectionally, A−T+ had similar tau-PET uptake to individuals with an A−T− biomarker profile.</jats:p></jats:sec><jats:sec id="ab-noi230049-10"><jats:title>Conclusion and Relevance</jats:title><jats:p>Results suggest that the CSF A−T+ biomarker profile was found in approximately 5% 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></jats:sec>

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