Ossenkoppele Rik, Coomans Emma M, Apostolova Liana G, Baker Suzanne L, Barthel Henryk, Beach Thomas G, Benzinger Tammy L S, Betthauser Tobey, Bischof Gérard N, Bottlaender Michel, Bourgeat Pierick, den Braber Anouk, Brendel Matthias, Brickman Adam M, Cash David M, Carrillo Maria C, Coath William, Christian Bradley T, Dickerson Brad C, Dore Vincent, Drzezga Alexander, Feizpour Azadeh, van der Flier Wiesje M, Franzmeier Nicolai, Frisoni Giovanni B, Garibotto Valentina, van de Giessen Elsmarieke, Domingo-Gispert Juan, Gnoerich Johannes, Gu Yuna, Guan Yihui, Hanseeuw Bernard J, Harrison Theresa M, Jack Clifford R, Jaeger Elena, Jagust William J, Jansen Willemijn J, La Joie Renaud, Johnson Keith A, Johnson Sterling C, Kennedy Ian A, Kim Jun Pyo, van Laere Koen, Lagarde Julien, Lao Patrick, Luchsinger José A, Kern Silke, Kreisl William C, Malotaux Vincent, Malpetti Maura, Manly Jennifer J, Mao Xiaoxie, Mattsson-Carlgren Niklas, Messerschmidt Konstantin, Minguillon Carolina, Mormino Elizabeth M, O'Brien John T, Palmqvist Sebastian, Peretti Debora E, Petersen Ron C, Pijnenburg Yolande A L, Pontecorvo Michael J, Poirier Judes, Rabinovici Gil D, Rahmouni Nesrine, Risacher Shannon L, Rosa-Neto Pedro, Rosen Howard, Rowe Christopher C, Rowe James B, Rullmann Michael, Salman Yasmine, Sarazin Marie, Saykin Andrew J, Schneider Julie A, Schöll Michael, Schott Jonathan M, Seo Sang Won, Serrano Geidy E, Shcherbinin Sergey, Shekari Mahnaz, Skoog Ingmar, Smith Ruben, Sperling Reisa A, Spruyt Laure, Stomrud Erik, Strandberg Olof, Therriault Joseph, Xie Fang, Vandenberghe Rik, Villemagne Victor L, Villeneuve Sylvia, Visser Pieter Jelle, Vossler Hillary, Young Christina B, Groot Colin, Hansson Oskar
Clinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.
Alzheimer Center Amsterdam, Neurology, Amsterdam UMC; location VUmc, Amsterdam, The Netherlands.
Nat Neurosci. 2025 Jul 16. doi: 10.1038/s41593-025-02000-6.
Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia. We found that from age 60 years to 80 years, tau PET positivity in a temporal composite region increased from 1.1% to 4.4% among CU amyloid-β (Aβ)-negative participants and from 17.4% to 22.2% among CU Aβ-positive participants. Across the same age span, tau PET positivity decreased from 68.0% to 52.9% in participants with MCI and from 91.5% to 74.6% in participants with dementia. Age, Aβ status, APOE ε4 carriership and female sex were all associated with a higher prevalence of tau PET positivity across groups. APOE ε4 carriership in CU individuals lowered the age at onset of both Aβ positivity and tau positivity by decades. Finally, we replicated these associations in an independent autopsy dataset (N = 5,072 from 3 cohorts).
tau正电子发射断层扫描（PET）成像能够在体内检测阿尔茨海默病中的tau蛋白病，这与神经退行性变和认知衰退相关。了解人口统计学、临床和遗传因素如何与tau PET阳性相关，将有助于其在临床实践和研究中的应用。在此，我们对全球42个队列（N = 12,048）进行了分析，其中包括7394名认知未受损（CU）参与者、2177名轻度认知障碍（MCI）参与者和2477名痴呆症参与者。我们发现，在60岁至80岁之间，CU淀粉样β蛋白（Aβ）阴性参与者中，颞叶复合区域的tau PET阳性率从1.1%升至4.4%，而CU Aβ阳性参与者中则从17.4%升至22.2%。在相同年龄范围内，MCI参与者的tau PET阳性率从68.0%降至52.9%，痴呆症参与者则从91.5%降至74.6%。年龄、Aβ状态、APOE ε4携带者状态和女性性别在所有组中均与tau PET阳性的较高患病率相关。CU个体中的APOE ε4携带者状态使Aβ阳性和tau阳性的发病年龄降低了数十年。最后，我们在一个独立的尸检数据集（来自3个队列，N = 5072）中重复了这些关联。
