N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits.
N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits.
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DOI：
10.1007/s00401-013-1129-2
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发表时间：
2013-08
影响因子：
12.7
通讯作者：
Bayer TA
中科院分区：
文献类型：
--
作者：
Bouter Y;Dietrich K;Wittnam JL;Rezaei-Ghaleh N;Pillot T;Papot-Couturier S;Lefebvre T;Sprenger F;Wirths O;Zweckstetter M;Bayer TA
n -截断的a - β4-42在阿尔茨海默病（AD）脑组织中含量丰富，是第一个在AD斑块中发现的a - β肽。然而，在AD病因学中可能起的作用在很大程度上被忽视了。在本报告中，我们证明了a - β4-42在单体消耗和低聚物形成方面迅速形成具有高聚集倾向的聚集体。短期处理初级皮质神经元表明，Aβ4-42与焦谷氨酸Aβ3-42和Aβ1-42具有相同的毒性。与这些发现一致，使用脑室内Aβ注射治疗野生型小鼠，Aβ4-42、焦谷氨酸Aβ3-42和Aβ1-42诱导了显著的工作记忆缺陷。表达a - β4-42的转基因小鼠（Tg4-42转基因系）在海马中出现大量CA1锥体神经元丢失。海马特异性表达a - β4-42与Morris水迷宫测试评估的年龄依赖性空间参考记忆缺陷有良好的相关性。我们的研究结果表明，n -截断的a - β4-42引发急性和长期的行为缺陷，与AD典型的记忆功能障碍相当。
N-truncated Aβ4-42 is highly abundant in Alzheimer disease (AD) brain and was the first Aβ peptide discovered in AD plaques. However, a possible role in AD aetiology has largely been neglected. In the present report, we demonstrate that Aβ4-42 rapidly forms aggregates possessing a high aggregation propensity in terms of monomer consumption and oligomer formation. Short-term treatment of primary cortical neurons indicated that Aβ4-42 is as toxic as pyroglutamate Aβ3-42 and Aβ1-42. In line with these findings, treatment of wildtype mice using intraventricular Aβ injection induced significant working memory deficits with Aβ4-42, pyroglutamate Aβ3-42 and Aβ1-42. Transgenic mice expressing Aβ4-42 (Tg4-42 transgenic line) developed a massive CA1 pyramidal neuron loss in the hippocampus. The hippocampus-specific expression of Aβ4-42 correlates well with age-dependent spatial reference memory deficits assessed by the Morris water maze test. Our findings indicate that N-truncated Aβ4-42 triggers acute and long-lasting behavioral deficits comparable to AD typical memory dysfunction.
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影响因子：
5.3
作者：
Brouillette, Jonathan;Caillierez, Raphaelle;Buee, Luc
通讯作者：
Buee, Luc
DOI：
10.1006/bbrc.2000.3490
发表时间：
2000-09-24
影响因子：
3.1
作者：
Harigaya, Y;Saido, TC;Younkin, SG
通讯作者：
Younkin, SG
影响因子：
12.7
作者：
Breyhan, Henning;Wirths, Oliver;Bayer, Thomas A.
通讯作者：
Bayer, Thomas A.
影响因子：
16.6
作者：
Haupt, Christian;Leppert, Joerg;Faendrich, Marcus
通讯作者：
Faendrich, Marcus
影响因子：
6
作者：
Casas, C;Sergeant, N;Pradier, L
通讯作者：
Pradier, L