Tau seeding in chronic traumatic encephalopathy parallels disease severity.
Tau seeding in chronic traumatic encephalopathy parallels disease severity.
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DOI：
10.1007/s00401-021-02373-5
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发表时间：
2021-12
影响因子：
12.7
通讯作者：
Diamond MI
中科院分区：
文献类型：
--
作者：
Kaufman SK;Svirsky S;Cherry JD;McKee AC;Diamond MI
慢性创伤性脑病 (CTE) 是一种神经退行性 tau 蛋白病，与行为、情绪和认知障碍（包括痴呆）有关。 tau蛋白病是神经退行性疾病，其神经病理学表型以tau蛋白病理学的独特组织病理学特征为特征，tau蛋白病理学逐渐沉积在整个大脑中。在某些 tau 蛋白病中，尤其是阿尔茨海默病 (AD)，tau 蛋白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 蛋白病理学的进展可以通过 tau 蛋白种子来解释，tau 蛋白种子采用不同的构象并充当自身扩增的模板，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，可以有效地检测 Tau 种子，该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)。生物传感器能够对固定和新鲜冷冻脑组织中的 tau 蛋白播种进行定量。 CTE 中的 Phospho-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。我们使用一种既定的生物传感器测定法，对 27 名 CTE 患者、5 名其他 tau 病患者和 5 名阴性对照患者 11 个脑区的固定组织薄切片中的 tau 接种进行独立量化，并与 AT8 磷酸化 tau 组织病理学进行比较。与之前的 AD 研究相比，我们在 CTE 过程的后期（主要是 III 期和 IV 期）检测到了 tau 蛋白播种。它在解剖学上不如 AT8 阳性包涵体普遍，而 AT8 阳性包涵体相对广泛。我们特别观察到边缘系统（杏仁核、丘脑、基底神经节）中的播种，这可能解释了 CTE 的主要认知和行为障碍。
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.
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影响因子：
4.3
作者：
DeVos SL;Corjuc BT;Oakley DH;Nobuhara CK;Bannon RN;Chase A;Commins C;Gonzalez JA;Dooley PM;Frosch MP;Hyman BT
通讯作者：
Hyman BT
影响因子：
16.2
作者：
Kaufman SK;Sanders DW;Thomas TL;Ruchinskas AJ;Vaquer-Alicea J;Sharma AM;Miller TM;Diamond MI
通讯作者：
Diamond MI
DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
影响因子：
3.2
作者：
Bieniek KF;Cairns NJ;Crary JF;Dickson DW;Folkerth RD;Keene CD;Litvan I;Perl DP;Stein TD;Vonsattel JP;Stewart W;Dams-O'Connor K;Gordon WA;Tripodis Y;Alvarez VE;Mez J;Alosco ML;McKee AC;TBI/CTE Research Group
通讯作者：
TBI/CTE Research Group
影响因子：
17.1
作者：
Goldstein LE;Fisher AM;Tagge CA;Zhang XL;Velisek L;Sullivan JA;Upreti C;Kracht JM;Ericsson M;Wojnarowicz MW;Goletiani CJ;Maglakelidze GM;Casey N;Moncaster JA;Minaeva O;Moir RD;Nowinski CJ;Stern RA;Cantu RC;Geiling J;Blusztajn JK;Wolozin BL;Ikezu T;Stein TD;Budson AE;Kowall NW;Chargin D;Sharon A;Saman S;Hall GF;Moss WC;Cleveland RO;Tanzi RE;Stanton PK;McKee AC
通讯作者：
McKee AC