Massachusetts General Hospital, Boston, MA 02114, USA.
Harvard Medical School, Boston, MA 02115, USA.
Sci Transl Med. 2021 Jan 20;13(577). doi: 10.1126/scitranslmed.abc0655.
Advances in molecular positron emission tomography (PET) have enabled anatomic tracking of brain pathology in longitudinal studies of normal aging and dementia, including assessment of the central model of Alzheimer's disease (AD) pathogenesis, according to which TAU pathology begins focally but expands catastrophically under the influence of amyloid-β (Aβ) pathology to mediate neurodegeneration and cognitive decline. Initial TAU deposition occurs many years before Aβ in a specific area of the medial temporal lobe. Building on recent work that enabled focus of molecular PET measurements on specific TAU-vulnerable convolutional temporal lobe anatomy, we applied an automated anatomic sampling method to quantify TAU PET signal in 443 adult participants from several observational studies of aging and AD, spanning a wide range of ages, Aβ burdens, and degrees of clinical impairment. We detected initial cortical emergence of tauopathy near the rhinal sulcus in clinically normal people and, in a subset with longitudinal 2-year follow-up data ( = 104), tracked Aβ-associated spread of TAU from this site first to nearby neocortex of the temporal lobe and then to extratemporal regions. Greater rate of TAU spread was associated with baseline measures of both global Aβ burden and medial temporal lobe TAU. These findings are consistent with clinicopathological correlation studies of Alzheimer's tauopathy and enable precise tracking of AD-related TAU progression for natural history studies and prevention therapeutic trials.
分子正电子发射断层扫描 (PET) 的进展使得能够在正常衰老和痴呆症的纵向研究中对脑病理学进行解剖追踪，包括评估阿尔茨海默病 (AD) 发病机制的中心模型，根据该模型，tau 病理学首先在局部开始，但在淀粉样蛋白-β (Aβ) 病理学的影响下灾难性地扩展，介导神经退行性变和认知能力下降。tau 沉积物最初出现在内侧颞叶的特定区域，比 Aβ 早多年。基于最近的一项工作，该工作使得能够将分子 PET 测量重点集中在特定的 tau 易损性卷积颞叶解剖结构上，我们应用了一种自动解剖采样方法来量化来自几个衰老和 AD 观察性研究的 443 名成年参与者的 tau PET 信号，这些研究涵盖了广泛的年龄、Aβ 负担和临床损伤程度。我们在临床正常人群中检测到了靠近嗅沟的 tau 病的初始皮质出现，并且在具有 2 年纵向随访数据的亚组中（= 104），从该部位首先追踪到了与 Aβ 相关的 tau 从颞叶附近的新皮质扩散，然后扩散到颞叶以外的区域。tau 扩散的速度越快，与全局 Aβ 负担和内侧颞叶 tau 的基线测量值越高。这些发现与阿尔茨海默氏 tau 病的临床病理相关性研究一致，并为自然史研究和预防治疗试验实现了 AD 相关 tau 进展的精确追踪。
