Chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy, is associated with behavioral, mood and cognitive impairment, including dementia. Tauopathies are neurodegenerative diseases whose neuropathological phenotypes are characterized by distinct histopathologic features of tau pathology, which progressively deposit throughout the brain. In certain tauopathies, especially Alzheimer’s disease (AD), tau deposition appears to follow brain network connections. Experimental evidence suggests that the progression of tau pathology in humans, mouse and cell models could be explained by tau seeds that adopt distinct conformations and serve as templates for their own amplification to mediate transcellular propagation of pathology. Tau seeds are efficiently detected by the induction of aggregation in cell-based “biosensors” that express tau repeat domain (RD) with a disease-associated mutation (P301S) fused to complementary fluorescent protein tags (cyan and yellow fluorescent protein). Biosensors enable quantification of tau seeding in fixed and fresh-frozen brain tissue. Phospho-tau deposition in CTE follows progressive stages (I–IV), but the relationship of seeding to this deposition is unclear. We have used an established biosensor assay to independently quantify tau seeding as compared to AT8 phospho-tau histopathology in thin sections of fixed tissues of 11 brain regions from 27 patients with CTE, 5 with other tauopathies, and 5 negative controls. In contrast to prior studies of AD, we detected tau seeding late in the course of CTE (predominantly stages III and IV). It was less anatomically prevalent than AT8-positive inclusions, which were relatively widespread. We especially observed seeding in the limbic system (amygdala, thalamus, basal ganglia), which may explain the dominant cognitive and behavior impairments that characterize CTE.

慢性创伤性脑病 (CTE) 是一种神经退行性 tau 病变，与行为、情绪和认知障碍（包括痴呆）有关。Tauopathies 是神经退行性疾病，其神经病理学表型以 tau 病理学的不同组织病理学特征为特征，其逐渐沉积在整个大脑中。在某些 tau 病变，尤其是阿尔茨海默病 (AD) 中，tau 沉积似乎遵循大脑网络连接。实验证据表明，人类、小鼠和细胞模型中 tau 病理学的进展可以通过 tau 种子来解释，这些 tau 种子采用不同的构象并作为自身扩增的模板，以介导病理学的跨细胞传播。通过在基于细胞的“生物传感器”中诱导聚集来有效检测 Tau 种子，这些“生物传感器”表达具有与互补荧光蛋白标签（青色和黄色荧光蛋白）融合的疾病相关突变 (P301S) 的 tau 重复结构域 (RD)。生物传感器能够量化固定和新鲜冷冻脑组织中的 tau 播种。CTE 中的磷酸化 tau 沉积遵循渐进阶段 (I-IV)，但播种与该沉积的关系尚不清楚。与来自 27 名 CTE 患者、5 名其他 tau 病患者和 5 名阴性对照的 11 个脑区固定组织的薄切片中的 AT8 磷酸化 tau 组织病理学相比，我们使用了已建立的生物传感器测定来独立量化 tau 播种。与先前的 AD 研究相比，我们在 CTE 过程的后期（主要是 III 和 IV 阶段）检测到 tau 播种。它在解剖学上不如 AT8 阳性包涵体那么普遍，后者相对普遍。我们特别观察到边缘系统（杏仁核、丘脑、基底神经节）的播种，这可以解释 CTE 的主要认知和行为障碍。