Titration of biologically active amyloid-β seeds in a transgenic mouse model of Alzheimer's disease.
Titration of biologically active amyloid-β seeds in a transgenic mouse model of Alzheimer's disease.
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DOI：
10.1038/srep09349
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发表时间：
2015-03-23
影响因子：
4.6
通讯作者：
Soto C
中科院分区：
文献类型：
--
作者：
Morales R;Bravo-Alegria J;Duran-Aniotz C;Soto C
动物模型中的实验证据表明，错误折叠的β淀粉样蛋白（Aβ）在疾病中遵循朊病毒样机制传播。感染性朊病毒的几种特性已被证明可诱导Aβ聚集体。然而，尚未进行Aβ错误折叠传递率的详细滴定和能够加速病理变化的生物活性Aβ种子的最低浓度估计。在这项研究中，将来自老年tg2576动物的脑提取物进行连续稀释，并将其脑内注射到来自同一转基因品系的年轻受试者体内。治疗后几个月处死动物，分析脑切片的淀粉样蛋白病理学。我们观察到，给予错误折叠的Aβ能够显著加速年轻小鼠中的淀粉样蛋白沉积，即使原始样品被稀释了一百万倍。将本实验中获得的滴定曲线与这些小鼠随时间自发蓄积的天然Aβ负荷进行比较。我们的研究结果表明，给予最大剂量的Aβ种子导致病理学加速，相当于一年多。这些结果表明，脑中存在的活性Aβ种子可以以可滴定的方式接种淀粉样变性，与感染性朊病毒的观察结果相似。
Experimental evidence in animal models suggests that misfolded Amyloid-β (Aβ) spreads in disease following a prion-like mechanism. Several properties characteristics of infectious prions have been shown for the induction of Aβ aggregates. However, a detailed titration of Aβ misfolding transmissibility and estimation of the minimum concentration of biologically active Aβ seeds able to accelerate pathological changes has not yet been performed. In this study, brain extracts from old tg2576 animals were serially diluted and intra-cerebrally injected into young subjects from the same transgenic line. Animals were sacrificed several months after treatment and brain slices were analyzed for amyloid pathology. We observed that administration of misfolded Aβ was able to significantly accelerate amyloid deposition in young mice, even when the original sample was diluted a million times. The titration curve obtained in this experiment was compared to the natural Aβ load spontaneously accumulated by these mice overtime. Our findings suggest that administration of the largest dose of Aβ seeds led to an acceleration of pathology equivalent to over a year. These results show that active Aβ seeds present in the brain can seed amyloidosis in a titratable manner, similarly as observed for infectious prions.
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影响因子：
3.8
作者：
KIMBERLIN, RH;WALKER, CA
通讯作者：
WALKER, CA
影响因子：
4.7
作者：
Rosen RF;Fritz JJ;Dooyema J;Cintron AF;Hamaguchi T;Lah JJ;LeVine H 3rd;Jucker M;Walker LC
通讯作者：
Walker LC
影响因子：
56.9
作者：
Meyer-Luehmann, Melanie;Coomaraswamy, Janaky;Jucker, Mathias
通讯作者：
Jucker, Mathias
DOI：
10.1016/j.bbrc.2008.09.141
发表时间：
2008-12-12
影响因子：
3.1
作者：
Morales, Rodrigo;Buytaert-Hoefen, Kimberley A.;Soto, Claudio
通讯作者：
Soto, Claudio
可传播的蛋白质：扩大王室异端。
影响因子：
64.5
作者：
Soto C
通讯作者：
Soto C