Hojjati Seyed Hani, Chiang Gloria C, Butler Tracy A, Chen Kewei, Khalafi Mohammad, Yazdi Bardiya Ghaderi, Foldi Nancy, Nayak Siddharth, de Leon Mony, Li Yi, Stern Yaakov, Luchsinger José A, Razlighi Qolamreza R
Department of Radiology, Brain Health Imaging Institute, Weill Cornell Medicine, New York, New York, USA.
College of Health Solutions, Arizona State University, Phoenix, Arizona, USA.
Alzheimers Dement. 2025 May;21(5):e70153. doi: 10.1002/alz.70153.
The spatial heterogeneity of tau deposition is closely linked to clinical variants of Alzheimer's disease (AD). Detecting these patterns in the preclinical stage is challenging, but second-generation tau tracers provide a unique opportunity to do so.
We used independent component analysis (ICA) and tau positron emission tomography (PET) imaging with the 18F-MK6240 tracer in 590 cognitively healthy adults (mean age 66.58 ± 5.13 years, 340 females) to identify tau patterns in the preclinical stage.
Using all individuals, seven distinct patterns emerged, with medial temporal lobe (MTL) involvement associated with age, Aβ burden, apolipoprotein E (APOE) genotype, and plasma total tau. Bilateral amygdala-hippocampus tau deposition was associated negatively with memory (t = -2.64, p < 0.01), while broader neocortical patterns, especially asymmetric ones, were linked to deficits in language (t < -3.13, p < 0.002) and reasoning (t < -2.63, p < 0.01).
These findings advance our understanding of preclinical tau heterogeneity, offering new insights for early AD intervention.
Seven tau deposition patterns were identified in preclinical stages of AD, including medial temporal lobe and asymmetric neocortical patterns. Medial temporal lobe patterns were strongly linked to age, APOE genotype, Aβ burden, and plasma total tau levels. Neocortical patterns, especially asymmetric ones, were linked to domain-specific cognitive deficits, notably in language and reasoning. This research highlights the potential of using tau deposition patterns for early detection and tailoring interventions in preclinical AD.
tau蛋白沉积的空间异质性与阿尔茨海默病（AD）的临床变异密切相关。在临床前阶段检测这些模式具有挑战性，但第二代tau蛋白示踪剂提供了这样做的独特机会。
我们对590名认知健康的成年人（平均年龄66.58±5.13岁，340名女性）使用独立成分分析（ICA）和18F-MK6240示踪剂进行tau正电子发射断层扫描（PET）成像，以识别临床前阶段的tau蛋白模式。
在所有个体中，出现了七种不同的模式，内侧颞叶（MTL）受累与年龄、淀粉样β蛋白（Aβ）负担、载脂蛋白E（APOE）基因型和血浆总tau蛋白相关。双侧杏仁核-海马体tau蛋白沉积与记忆力呈负相关（t=-2.64，p<0.01），而更广泛的新皮质模式，尤其是不对称模式，与语言（t<-3.13，p<0.002）和推理（t<-2.63，p<0.01）缺陷有关。
这些发现推进了我们对临床前tau蛋白异质性的理解，为早期AD干预提供了新的见解。
在AD的临床前阶段识别出七种tau蛋白沉积模式，包括内侧颞叶和不对称新皮质模式。内侧颞叶模式与年龄、APOE基因型、Aβ负担和血浆总tau蛋白水平密切相关。新皮质模式，尤其是不对称模式，与特定领域的认知缺陷有关，特别是在语言和推理方面。这项研究突出了利用tau蛋白沉积模式在临床前AD中进行早期检测和定制干预的潜力。
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