Exogenous seeding of cerebral β-amyloid deposition in βAPP-transgenic rats.
Exogenous seeding of cerebral β-amyloid deposition in βAPP-transgenic rats.
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DOI：
10.1111/j.1471-4159.2011.07551.x
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发表时间：
2012-03
影响因子：
4.7
通讯作者：
Walker LC
中科院分区：
文献类型：
--
作者：
Rosen RF;Fritz JJ;Dooyema J;Cintron AF;Hamaguchi T;Lah JJ;LeVine H 3rd;Jucker M;Walker LC
在Aβ前体蛋白转基因小鼠脑内注射含有聚集Aβ种子的稀释脑提取物可刺激老年斑中Aβ肽的沉积和脑Aβ血管病变。越来越多的证据表明，在这种现象中存在一种类似朊病毒的腐败蛋白模板机制，其中聚集的a β本身就是种子。与朊病毒疾病不同，朊病毒疾病可以在不太可能自发发病的动物中从头诱导，先前的Aβ播种实验使用的动物模型随着年龄的增长，最终会在没有播种的情况下产生Aβ病变。在本研究中，我们首先建立了表达人a β前体蛋白的转基因大鼠模型（APP21系）在其中位寿命（30个月）内不表现内源性a β沉积。接下来，我们在3个月大的APP21大鼠海马内注射含有聚集Aβ的稀释阿尔茨海默病脑提取物。在9个月的潜伏期后，这些大鼠在注射海马中出现老年斑和脑a β血管病变，而对照组大鼠则没有这些病变。这些发现强调了药物和宿主在控制种子蛋白聚集方面的共同依赖性，并表明即使在相对难以自发形成Aβ实质和血管沉积的动物中，也可以诱导脑Aβ-淀粉样变性。
Deposition of the Aβ peptide in senile plaques and cerebral Aβ angiopathy can be stimulated in Aβ-precursor protein-transgenic mice by the intracerebral injection of dilute brain extracts containing aggregated Aβ seeds. Growing evidence implicates a prion-like mechanism of corruptive protein templating in this phenomenon, in which aggregated Aβ itself is the seed. Unlike prion disease, which can be induced de novo in animals that are unlikely to spontaneously develop the disease, previous experiments with Aβ seeding have employed animal models that, as they age, eventually will generate Aβ lesions in the absence of seeding. In the present study, we first established that a transgenic rat model expressing human Aβ-precursor protein (APP21 line) does not manifest endogenous deposits of Aβ within the course of its median lifespan (30 months). Next, we injected 3-month-old APP21 rats intrahippocampally with dilute Alzheimer brain extracts containing aggregated Aβ. After a 9-month incubation period, these rats had developed senile plaques and cerebral Aβ angiopathy in the injected hippocampus, whereas control rats remained free of such lesions. These findings underscore the co-dependence of agent and host in governing seeded protein aggregation, and show that cerebral Aβ-amyloidosis can be induced even in animals that are relatively refractory to the spontaneous origination of parenchymal and vascular deposits of Aβ.
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DOI：
10.1523/jneurosci.3088-11.2011
发表时间：
2011-10-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Langer F;Eisele YS;Fritschi SK;Staufenbiel M;Walker LC;Jucker M
通讯作者：
Jucker M
影响因子：
56.9
作者：
Meyer-Luehmann, Melanie;Coomaraswamy, Janaky;Jucker, Mathias
通讯作者：
Jucker, Mathias
DOI：
10.1111/j.1432-1033.1993.tb19893.x
发表时间：
1993-01-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
OTVOS, L;SZENDREI, GI;MANTSCH, HH
通讯作者：
MANTSCH, HH
影响因子：
6.1
作者：
Liu, Li;Orozco, Ian J.;Duff, Karen
通讯作者：
Duff, Karen
影响因子：
6
作者：
Callahan, MJ;Lipinski, WJ;Walker, LC
通讯作者：
Walker, LC