Tau seeds occur before earliest Alzheimer's changes and are prevalent across neurodegenerative diseases.
Tau seeds occur before earliest Alzheimer's changes and are prevalent across neurodegenerative diseases.
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DOI：
10.1007/s00401-023-02574-0
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发表时间：
2023-07
影响因子：
12.7
通讯作者：
Kraus, Allison
中科院分区：
文献类型：
--
作者：
Manca, Matteo;Standke, Heidi G. G.;Browne, Danielle F. F.;Huntley, Mikayla L. L.;Thomas, Olivia R. R.;Orru, Christina D. D.;Hughson, Andrew G. G.;Kim, Yongya;Zhang, Jing;Tatsuoka, Curtis;Zhu, Xiongwei;Hiniker, Annie;Coughlin, David G. G.;Galasko, Douglas;Kraus, Allison
Tau神经元缠结是阿尔茨海默病神经病理学改变的标志。然而，在很大程度上仍然不清楚独特的阿尔茨海默病tau种子（即3R/4 R）如何与tau积累的组织学指标相关。此外，AD tau共同病理学被认为影响其他神经退行性疾病（包括路易体病）的特征和进展;然而，在此类疾病的背景下测量不同类型的tau种子是未满足的需求。在这里，我们使用tau实时振荡诱导转换（RT-QuIC）测定选择性定量额叶中的3R/4 R tau种子，其在AD神经病理变化的晚期疾病阶段积累组织学可识别的tau病理。在一系列神经退行性疾病病例和对照中的种子定量表明，在伴随的tau沉积的组织病理学指示之前，甚至在阿尔茨海默病相关的tau在脑中任何地方积累的最早证据之前，就可以很好地检测到tau播种活性。在AD的晚期，3R/4 R tau RT-QuIC测量与免疫组化tau负荷相关。此外，阿尔茨海默氏tau种子出现在本文评估的绝大多数病例中，包括原发性突触核蛋白病、额颞叶变性，甚至对照，尽管其水平比阿尔茨海默氏病例低多个对数。α-突触核蛋白播种活性证实了突触核蛋白病病例，并进一步表明α-突触核蛋白种子在一些阿尔茨海默病和原发性tau蛋白病病例中共同出现。我们的分析表明，中额叶中的3R/4 R tau种子与整体Braak分期和阿尔茨海默病神经病理学变化相关，支持tau RT-QuIC测定的定量预测价值。我们的数据还表明，在高（≥ IV）Braak阶段，女性的3R/4 R tau种子比男性高。这项研究表明，3R/4 R tau种子甚至在阿尔茨海默病变化的最早阶段之前就广泛存在，包括在正常甚至年轻个体中，在多种神经退行性疾病中普遍存在，以进一步定义疾病亚型。 在线版本包含补充材料，可通过10.1007/s 00401 -023-02574-0获得。
Tau neurofibrillary tangles are a hallmark of Alzheimer’s disease neuropathological change. However, it remains largely unclear how distinctive Alzheimer’s disease tau seeds (i.e. 3R/4R) correlate with histological indicators of tau accumulation. Furthermore, AD tau co-pathology is thought to influence features and progression of other neurodegenerative diseases including Lewy body disease; yet measurements of different types of tau seeds in the setting of such diseases is an unmet need. Here, we use tau real-time quaking-induced conversion (RT-QuIC) assays to selectively quantitate 3R/4R tau seeds in the frontal lobe which accumulates histologically identifiable tau pathology at late disease stages of AD neuropathologic change. Seed quantitation across a spectrum of neurodegenerative disease cases and controls indicated tau seeding activity can be detected well before accompanying histopathological indication of tau deposits, and even prior to the earliest evidence of Alzheimer’s-related tau accumulation anywhere in the brain. In later stages of AD, 3R/4R tau RT-QuIC measures correlated with immunohistochemical tau burden. In addition, Alzheimer’s tau seeds occur in the vast majority of cases evaluated here inclusive of primary synucleinopathies, frontotemporal lobar degeneration and even controls albeit at multi-log lower levels than Alzheimer’s cases. α-synuclein seeding activity confirmed synucleinopathy cases and further indicated the co-occurrence of α-synuclein seeds in some Alzheimer’s disease and primary tauopathy cases. Our analysis indicates that 3R/4R tau seeds in the mid-frontal lobe correlate with the overall Braak stage and Alzheimer’s disease neuropathologic change, supporting the quantitative predictive value of tau RT-QuIC assays. Our data also indicate 3R/4R tau seeds are elevated in females compared to males at high (≥ IV) Braak stages. This study suggests 3R/4R tau seeds are widespread even prior to the earliest stages of Alzheimer’s disease changes, including in normal, and even young individuals, with prevalence across multiple neurodegenerative diseases to further define disease subtypes. The online version contains supplementary material available at 10.1007/s00401-023-02574-0.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
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：
48
作者：
Irwin, David;Grossman, Murray;Weintraub, Daniel;Hurtig, Howard I.;Duda, John E.;Xie, Sharon X.;Lee, Edward B.;Van Deerlin, Vivianna M.;Lopez, Oscar L.;Kofler, Julia K.;Nelson, Peter T.;Jicha, Gregory A.;Woltjer, Randy;Quinn, Joseph F.;Kaye, Jeffery;Leverenz, James B.;Tsuang, Debby;Longfellow, Katelan;Yearout, Dora;Kukull, Walter;Keene, C. Dirk;Montine, Thomas J.;Zabetian, Cyrus P.;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
DOI：
10.1007/s12031-011-9589-0
发表时间：
2011-11
期刊：
Journal of molecular neuroscience : MN
影响因子：
--
作者：
Dickson DW;Kouri N;Murray ME;Josephs KA
通讯作者：
Josephs KA
影响因子：
14
作者：
通讯作者：
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