Moscoso Alexis, Heeman Fiona, Raghavan Sheelakumari, Costoya-Sánchez Alejandro, van Essen Martijn, Mainta Ismini, Camacho Valle, Rodríguez-Fonseca Omar, Silva-Rodríguez Jesús, Perissinotti Andrés, Gu Yuna, Yun Jihwan, Peretti Debora, Ribaldi Federica, Coomans Emma M, Brum Wagner S, Grothe Michel J, Aguiar Pablo, Bischof Gérard N, Drzezga Alexander, Seo Sang Won, Villeneuve Sylvia, Malpetti Maura, O'Brien John T, Rowe James B, van de Giessen Elsmarieke M, Ossenkoppele Rik, Jagust William J, Smith Ruben, Hansson Oskar, Frisoni Giovanni B, Garibotto Valentina, Soleimani-Meigooni David N, Carrillo Maria, Dickerson Bradford C, La Joie Renaud, Rabinovici Gil D, Apostolova Liana G, LaMontagne Pamela J, Pontecorvo Michael J, Johnson Keith A, Sperling Reisa A, Weiner Michael W, Petersen Ronald C, Jack Clifford R, Vemuri Prashanthi, Schöll Michael
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
JAMA. 2025 Jul 15;334(3):229-242. doi: 10.1001/jama.2025.7817.
Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD).
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.
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).
Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia).
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%).
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.
tau正电子发射断层扫描（PET）可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。
估计tau PET阳性的频率及其与临床结局相关的风险。
设计、设置和参与者：一项纵向研究，使用从21个队列汇总的数据，包括来自13个国家的6514名参与者的便利样本，数据收集于2013年1月至2024年6月之间。纳入认知未受损个体以及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。
使用氟代脱氧葡萄糖F 18进行tau PET检查、淀粉样β蛋白（Aβ）PET检查以及临床检查。根据美国食品药品监督管理局和欧洲药品管理局批准的方法，对tau PET扫描进行视觉评分，该方法旨在表明存在晚期神经原纤维缠结病理（Braak分期V-VI期）。
tau PET阳性的频率以及临床进展（如进展为MCI或痴呆）的绝对风险。
在6514名参与者（平均年龄69.5岁；50.5%为女性）中，中位随访时间为1.5至4.0年。在3487名认知未受损参与者中，349名（9.8%）tau PET呈阳性；年龄小于50岁者中tau PET阳性的估计频率小于1%，60岁时为3%（95%CI，2%-4%），90岁时增至19%（95%CI，16%-24%）。tau PET阳性频率估计值在MCI和AD痴呆临床诊断中均有所增加（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%）Aβ PET也呈阳性。与Aβ PET阳性/tau PET阴性（17%[95%CI，13%-22%]）和Aβ PET阴性/tau PET阴性（6%[95%CI，5%-8%]）个体相比，Aβ PET和tau PET均呈阳性的认知未受损参与者在接下来5年进展为MCI或痴呆的绝对风险更高（57%[95%CI，45%-71%]）。在进行tau PET扫描时为MCI的参与者中，Aβ PET阳性/tau PET阳性的情况与5年进展为痴呆的绝对风险70%（95%CI，59%-81%）相关。
在一个大型便利样本中，认知未受损个体中tau PET扫描呈阳性的发生率不可忽视，Aβ PET阳性与tau PET阳性的组合在AD的临床前期和症状期均与高临床进展风险相关。这些发现强调了tau PET作为AD病理分期生物标志物的潜力。
