N-truncated Aβ(4-x) peptides in sporadic Alzheimer's disease cases and transgenic Alzheimer mouse models.
N-truncated Aβ(4-x) peptides in sporadic Alzheimer's disease cases and transgenic Alzheimer mouse models.
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DOI：
10.1186/s13195-017-0309-z
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发表时间：
2017-10-04
期刊：
影响因子：
--
通讯作者：
Weggen S
中科院分区：
文献类型：
--
作者：
Wirths O;Walter S;Kraus I;Klafki HW;Stazi M;Oberstein TJ;Ghiso J;Wiltfang J;Bayer TA;Weggen S
神经毒性淀粉样β（Aβ）肽在脑实质和脑血管斑块中的沉积被认为是阿尔茨海默病（AD）发病机制中的关键事件。尽管已对全长Aβ肽（如Aβ1-40和Aβ1-42）的存在和影响进行了广泛分析，但N端截短Aβ肽物质的沉积受到的关注要少得多，这主要是因为缺乏特异性抗体。本文描述了针对Aβ4-x肽的新型选择性抗体的制备和表征，并提供了Aβ4-x在人脑中及其在APP/PS1 KI和5XFAD转基因小鼠模型中分布的免疫组织化学证据。在AD和唐氏综合征病例以及两种AD小鼠模型中，Aβ4-x染色模式主要局限于淀粉样斑块核心和脑淀粉样血管病。相反，弥漫性淀粉样沉积物对Aβ4-x免疫反应性基本呈阴性。未观察到明显的神经元内染色。本研究的结果与先前的报告一致，证明Aβ4-x肽具有高聚集倾向，并表明这些N-截短的Aβ物质在淀粉样蛋白生成和斑块核心形成过程中发挥重要作用。本文的在线版本（doi：10.1186/s13195-017-0309-z）包含补充材料，可供授权用户使用。
The deposition of neurotoxic amyloid-β (Aβ) peptides in plaques in the brain parenchyma and in cerebral blood vessels is considered to be a key event in Alzheimer’s disease (AD) pathogenesis. Although the presence and impact of full-length Aβ peptides such as Aβ1–40 and Aβ1–42 have been analyzed extensively, the deposition of N-terminally truncated Aβ peptide species has received much less attention, largely because of the lack of specific antibodies. This paper describes the generation and characterization of novel antibodies selective for Aβ4–x peptides and provides immunohistochemical evidence of Aβ4–x in the human brain and its distribution in the APP/PS1KI and 5XFAD transgenic mouse models. The Aβ4–x staining pattern was restricted mainly to amyloid plaque cores and cerebral amyloid angiopathy in AD and Down syndrome cases and in both AD mouse models. In contrast, diffuse amyloid deposits were largely negative for Aβ4–x immunoreactivity. No overt intraneuronal staining was observed. The findings of this study are consistent with previous reports demonstrating a high aggregation propensity of Aβ4–x peptides and suggest an important role of these N-truncated Aβ species in the process of amyloidogenesis and plaque core formation. The online version of this article (doi:10.1186/s13195-017-0309-z) contains supplementary material, which is available to authorized users.
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影响因子：
12.7
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
通讯作者：
Bayer TA
DOI：
10.1186/alzrt121
发表时间：
2012-05-23
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Moore BD;Chakrabarty P;Levites Y;Kukar TL;Baine AM;Moroni T;Ladd TB;Das P;Dickson DW;Golde TE
通讯作者：
Golde TE
影响因子：
4.7
作者：
Beher, D;Wrigley, JDJ;Shearman, MS
通讯作者：
Shearman, MS
DOI：
10.1186/alzrt258
发表时间：
2014
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Kummer MP;Heneka MT
通讯作者：
Heneka MT
影响因子：
4.8
作者：
Bien, Jessica;Jefferson, Tamara;Pietrzik, Claus U.
通讯作者：
Pietrzik, Claus U.