Prevalence and Clinical Implications of a β-Amyloid-Negative, Tau-Positive Cerebrospinal Fluid Biomarker Profile in Alzheimer Disease.
Prevalence and Clinical Implications of a β-Amyloid-Negative, Tau-Positive Cerebrospinal Fluid Biomarker Profile in Alzheimer Disease.
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DOI：
10.1001/jamaneurol.2023.2338
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发表时间：
2023-07-31
期刊：
影响因子：
29
通讯作者：
Zetterberg, Henrik
中科院分区：
文献类型：
--
作者：
Erickson, Pontus;Simren, 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
这项队列研究评估了具有β-淀粉样蛋白阴性、tau蛋白阳性脑脊液生物标志物特征的个体的记忆临床患病率和预后。具有β-淀粉样蛋白阴性、tau蛋白阳性（A-T+）脑脊液（CSF）特征的个体的记忆临床患病率和预后如何？在7679例患者的临床队列中，A-T + CSF的患病率为4.1%。纵向上，认知未受损的个体或轻度认知障碍和A-T + CSF特征的个体与A-T-CSF特征的个体在认知恶化、脑萎缩或脑葡萄糖代谢和正电子发射断层扫描指示的β-淀粉样蛋白负荷方面表现出相似的轨迹。A-T+的CSF特征似乎是良性的，尽管被指南归类为病理变化;与生物标志物阴性CSF的个体相比，A-T + CSF的个体没有更高的认知能力下降率或更快的疾病进展。缺乏对β-淀粉样蛋白阴性、tau蛋白阳性（A-T+）脑脊液（CSF）生物标志物谱个体的患病率和预后的了解。估计CSF A-T+生物标志物谱的患病率并研究其临床意义。这是一项对哥德堡大学（UGOT）队列进行的横断面多中心回顾性队列研究（2019年11月至2021年1月），纵向多中心阿尔茨海默病神经影像学倡议（ADNI）队列（轻度认知障碍[MCI]和无认知障碍的个体; 2005年9月-2022年5月），以及2个威斯康星州队列，威斯康星州阿尔茨海默病研究中心和威斯康星州阿尔茨海默病预防登记处（WISC;无认知障碍的个体; 2007年2月至2020年11月）。这是一项多中心研究，数据收集自临床常规（UGOT）和研究环境（ADNI和WISC）的转诊中心。合格个体接受1次腰椎穿刺（所有队列）、2次或2次以上认知评估（ADNI和WISC）和2次单独的成像（仅ADNI）。数据分析于2022年8月至2023年4月进行。基线CSF Aβ42/40和磷酸化tau（p-tau）181;认知测试（ADNI：改良临床前阿尔茨海默认知复合终点[mPACC]; WISC：改良3-测试PACC [PACC-3]）。ADNI队列中的暴露包括[18 F]-florbetapir淀粉样蛋白正电子发射断层扫描（PET）、磁共振成像（MRI）、[18 F]-氟脱氧葡萄糖PET（FDG-PET）和横断面tau-PET（ADNI：[18 F]-flortaucipir，WISC：[18 F]-MK 6240）。主要结局为A-T + vs A-T-组中CSF AT生物标志物特征的患病率和连续纵向整体认知结局和成像生物标志物轨迹。次要结局包括横断面tau-PET。共计7679人（平均[SD]年龄，71.0 [8.4]岁; 4101名男性[53%]）被纳入UGOT队列，970名个体（平均[SD]年龄，73 [7.0]岁; 526名男性[54%]）被纳入ADNI队列，（平均[SD]年龄，60 [7.3]岁; 346名女性[67%]）被纳入WISC队列。UGOT队列中A-T+的患病率为4.1%（95% CI，3.7%-4.6%），比其他模式更不常见。纵向上，在认知或成像生物标志物的A-T+和A-T-曲线之间未观察到恶化率的显著差异。在横断面上，A-T+与具有A-T-生物标志物特征的个体具有相似的tau-PET摄取。结果表明，在大约5%的腰椎穿刺中发现了CSF A-T+生物标志物特征，与生物标志物阴性个体相比，该特征与更高的认知能力下降率或疾病进展的生物标志物体征无关。
This cohort study assesses the memory clinic prevalence and prognosis of individuals with a β-amyloid–negative, tau-positive cerebrospinal fluid biomarker profile. What is the memory clinic prevalence and prognosis of individuals who have a β-amyloid–negative, tau-positive (A−T+) cerebrospinal fluid (CSF) profile? In a clinical cohort of 7679 individuals, prevalence of A−T+ CSF was 4.1%. Longitudinally, cognitively unimpaired individuals or individuals with mild cognitive impairment and an A−T+ CSF profile exhibited similar trajectories to individuals with an A−T− CSF profile in relation to cognitive deterioration, brain atrophy, or cerebral glucose metabolism and β-amyloid burden indexed by positron emission tomography. A CSF profile of A−T+ appears to be benign despite being classified as a pathologic change by guidelines; compared with individuals with biomarker-negative CSF, individuals with A−T+ CSF do not have higher rates of cognitive decline or faster disease progression. Knowledge is lacking on the prevalence and prognosis of individuals with a β-amyloid–negative, tau-positive (A−T+) cerebrospinal fluid (CSF) biomarker profile. To estimate the prevalence of a CSF A−T+ biomarker profile and investigate its clinical implications. 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. 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 [18F]-florbetapir amyloid positron emission tomography (PET), magnetic resonance imaging (MRI), [18F]-fluorodeoxyglucose PET (FDG-PET), and cross-sectional tau-PET (ADNI: [18F]-flortaucipir, WISC: [18F]-MK6240). 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. 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. 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.
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影响因子：
29
作者：
Donohue, Michael C.;Sperling, Reisa A.;Salmon, David P.;Rentz, Dorene M.;Raman, Rema;Thomas, Ronald G.;Weiner, Michael;Aisen, Paul S.
通讯作者：
Aisen, Paul S.
影响因子：
9.9
作者：
Kern S;Zetterberg H;Kern J;Zettergren A;Waern M;Höglund K;Andreasson U;Wetterberg H;Börjesson-Hanson A;Blennow K;Skoog I
通讯作者：
Skoog I
DOI：
10.1016/j.jalz.2015.05.001
发表时间：
2015-07
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Jagust WJ;Landau SM;Koeppe RA;Reiman EM;Chen K;Mathis CA;Price JC;Foster NL;Wang AY
通讯作者：
Wang AY
影响因子：
11.1
作者：
Mattsson-Carlgren N;Janelidze S;Bateman RJ;Smith R;Stomrud E;Serrano GE;Reiman EM;Palmqvist S;Dage JL;Beach TG;Hansson O
通讯作者：
Hansson O
DOI：
10.1093/brain/awaa286
发表时间：
2020-12-05
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Mattsson-Carlgren N;Janelidze S;Palmqvist S;Cullen N;Svenningsson AL;Strandberg O;Mengel D;Walsh DM;Stomrud E;Dage JL;Hansson O
通讯作者：
Hansson O