瑞典隆德大学Oskar Hansson团队取得一项新突破。他们的研究显示，有认知障碍和无认知障碍人群中，Tau PET阳性随年龄、β-淀粉样蛋白状态、APOE基因型和性别而变化。这一研究成果于2025年7月16日发表在国际顶尖学术期刊《自然—神经科学》上。

在这里，该课题组人员对全球42个队列（N = 12048）进行了分析，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名痴呆参与者。该课题组研究人员发现从60岁开始80岁多年来，在CU淀粉样蛋白-β (a β)阴性的参与者中，tau PET在时间复合区域的阳性从1.1%增加到4.4%，在CU a β阳性的参与者中从17.4%增加到22.2%。在相同的年龄范围内，MCI参与者的tau PET阳性从68.0%下降到52.9%，痴呆参与者的tau PET阳性从91.5%下降到74.6%。年龄、a β状态、APOE ε4携带和女性性别均与tau PET阳性率升高相关。携带APOE ε4的CU个体的Aβ阳性和tau阳性的发病年龄都降低了几十年。最后，研究组在一个独立的尸检数据集中复制了这些关联（N=5072，来自3个队列)。

据了解，Tau正电子发射断层扫描（PET）成像允许在体内检测阿尔茨海默病中的Tau蛋白病变，这与神经变性和认知能力下降有关。了解人口统计学、临床和遗传因素与Tau PET阳性的关系将有助于其临床实践和研究的主题。

附：英文原文

Title: Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex

Author: Ossenkoppele, Rik, Coomans, Emma M., Apostolova, Liana G., Baker, Suzanne L., Barthel, Henryk, Beach, Thomas G., Benzinger, Tammy L. S., Betthauser, Tobey, Bischof, Grard 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, Jos A., Kern, Silke, Kreisl, William C., Malotaux, Vincent, Malpetti, Maura, Manly, Jennifer J., Mao, Xiaoxie, Mattsson-Carlgren, Niklas, Messerschmidt, Konstantin, Minguillon, Carolina

Issue&Volume: 2025-07-16

Abstract: 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 60years to 80years, 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).

DOI: 10.1038/s41593-025-02000-6

Source: https://www.nature.com/articles/s41593-025-02000-6