In vivo rate-determining steps of tau seed accumulation in Alzheimer's disease.
In vivo rate-determining steps of tau seed accumulation in Alzheimer's disease.
复制标题
在阿尔茨海默病中tau种子积累的体内速率决定步骤。
DOI：
10.1126/sciadv.abh1448
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发表时间：
2021-10-29
期刊：
影响因子：
13.6
通讯作者：
Klenerman D
中科院分区：
文献类型：
--
作者：
Meisl G;Hidari E;Allinson K;Rittman T;DeVos SL;Sanchez JS;Xu CK;Duff KE;Johnson KA;Rowe JB;Hyman BT;Knowles TPJ;Klenerman D
局部复制使阿尔茨海默病中的tau聚集体的数量每5年仅增加一次，从而限制了总体速率。蛋白质聚集体的复制及其在整个大脑中的扩散都与阿尔茨海默病（AD）的进展有关。然而，这些过程的速率是未知的，因此人类中的速率决定过程的身份仍然难以捉摸。通过将化学动力学与跨大脑区域的tau种子和聚集体的测量结合起来，我们可以量化它们在人脑中的复制率。值得注意的是，我们在几个不同的数据集中获得了可比的比率，从死后种子扩增测定到活体个体的tau PET研究，采用了五种不同的tau定量方法。我们的研究结果表明，从Braak阶段III开始，局部复制，而不是在大脑区域之间传播，是控制新皮层区域tau蛋白累积总体速率的主要过程。种子的数量每25年才翻一番。因此，限制局部复制可能是AD期间控制tau积累的最有希望的策略。
Local replication doubles the number of tau aggregate in Alzheimer’s disease only once every 5 years, limiting the overall rate. Both the replication of protein aggregates and their spreading throughout the brain are implicated in the progression of Alzheimer’s disease (AD). However, the rates of these processes are unknown and the identity of the rate-determining process in humans has therefore remained elusive. By bringing together chemical kinetics with measurements of tau seeds and aggregates across brain regions, we can quantify their replication rate in human brains. Notably, we obtain comparable rates in several different datasets, with five different methods of tau quantification, from postmortem seed amplification assays to tau PET studies in living individuals. Our results suggest that from Braak stage III onward, local replication, rather than spreading between brain regions, is the main process controlling the overall rate of accumulation of tau in neocortical regions. The number of seeds doubles only every ∼5 years. Thus, limiting local replication likely constitutes the most promising strategy to control tau accumulation during AD.
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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：
17.1
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通讯作者：
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作者：
Kundel F;Hong L;Falcon B;McEwan WA;Michaels TCT;Meisl G;Esteras N;Abramov AY;Knowles TJP;Goedert M;Klenerman D
通讯作者：
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影响因子：
16.2
作者：
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影响因子：
3.7
作者：
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