瑞典哥德堡大学Alexis Moscoso团队近日研究了Tau正电子发射断层扫描阳性的频率和临床预后。这一研究成果于2025年6月16日发表在《美国医学会杂志》上。

Tau正电子发射断层扫描（PET）允许在体内检测神经原纤维缠结，这是阿尔茨海默病（AD）的核心神经病理学特征。为了提供tau PET阳性频率及其临床结果相关风险的估计，研究组进行了一项纵向研究，使用来自21个队列的数据，包括2013年1月至2024年6月期间收集的来自13个国家的6514名参与者的便利样本。包括认知功能未受损的个人和临床诊断为轻度认知障碍（MCI）、AD痴呆或其他神经退行性疾病的患者。

暴露因素为Tau PET与flortaucipir F 18、淀粉样β（Aβ）PET和临床检查。根据美国食品和药物管理局和欧洲药品管理局批准的方法，Tau PET扫描被视觉评定为阳性，该方法旨在表明存在晚期神经纤维缠结病理（Braak V-VI期）。主要结局为tau PET阳性的频率和临床进展的绝对风险（例如，进展为MCI或痴呆症）。

在6514名参与者中（平均年龄69.5岁；50.5%为女性），中位随访时间为1.5至4.0年。在3487名认知功能未受损的参与者中，349名（9.8%）tau PET阳性；在50岁以下的人群中，tau PET阳性的估计频率小于1%，从60岁时的3%（95%CI，2%-4%）增加到90岁时的19%（95%CI16%-24%）。Tau PET阳性频率估计值在MCI和AD痴呆的临床诊断中有所增加（75岁时分别为43%[95%CI，41%-46%]和79%[95%CI、77%-82%）。大多数tau PET阳性个体（92%）也是AβPET阳性。与AβPET阳性/tau PET阴性（17%[95%CI，13%-22%]）和AβPET阴性/tau PET-阴性（6%[95%Cl，5%-8%]）个体相比，AβPET和tau PET均呈阳性的认知未受损参与者在未来5年内进展为MCI或痴呆症的绝对风险更高（57%[95%-CI，45%-71%]）。在tau PET扫描时患有MCI的参与者中，AβPET阳性/tau PET阳性与痴呆症进展的5年绝对风险70%相关（95%CI，59%-81%）。

综上，在一个大型便利样本中，在认知功能未受损的个体中，tau PET扫描呈阳性的比例不可忽视，aβPET阳性和tau PET阳性的组合与AD临床前和症状阶段的临床进展的高风险有关。这些发现强调了tau PET作为AD病理分期生物标志物的潜力。

附：英文原文

Title: Frequency and Clinical Outcomes Associated With Tau Positron Emission Tomography Positivity

Author: Alexis Moscoso, Fiona Heeman, Sheelakumari Raghavan, Alejandro Costoya-Sánchez, Martijn van Essen, Ismini Mainta, Valle Camacho, Omar Rodríguez-Fonseca, Jesús Silva-Rodríguez, Andrés Perissinotti, Yuna Gu, Jihwan Yun, Debora Peretti, Federica Ribaldi, Emma M. Coomans, Wagner S. Brum, Michel J. Grothe, Pablo Aguiar, Gérard N. Bischof, Alexander Drzezga, Sang Won Seo, Sylvia Villeneuve, Maura Malpetti, John T. O’Brien, James B. Rowe, Elsmarieke M. van de Giessen, Rik Ossenkoppele, William J. Jagust, Ruben Smith, Oskar Hansson, Giovanni B. Frisoni, Valentina Garibotto, David N. Soleimani-Meigooni, Maria Carrillo, Bradford C. Dickerson, Renaud La Joie, Gil D. Rabinovici, Liana G. Apostolova, Pamela J. LaMontagne, Michael J. Pontecorvo, Keith A. Johnson, Reisa A. Sperling, Michael W. Weiner, Ronald C. Petersen, Clifford R. Jack, Prashanthi Vemuri, Michael Schll, PREVENT-AD Research Group, the Harvard Aging Brain Study, the LEADS Consortium, and the Alzheimer’s Disease Neuroimaging Initiative, Angela Tam, Anne Labonte, Alexa Pichet Binette, Anne‐Marie Faubert

Issue&Volume: 2025-06-16

Abstract:

Importance  Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD).

Objective  To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes.

Design, Setting, and Participants  Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included.

Exposures  Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration– and European Medicines Agency–approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI).

Main Outcomes and Measures  Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia).

Results  Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET–positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET–positive/tau PET–negative (17% [95% CI, 13%-22%]) and Aβ PET–negative/tau PET–negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET–positive/tau PET–positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%).

Conclusions and Relevance  In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.

DOI: 10.1001/jama.2025.7817

Source: https://jamanetwork.com/journals/jama/fullarticle/2835393