Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, von-Siebold-Strasse 5, 37075, Goettingen, Germany.
Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, von-Siebold-Strasse 5, 37075, Goettingen, Germany.
Alzheimers Res Ther. 2017 Oct 4;9(1):80. doi: 10.1186/s13195-017-0309-z.
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 Aβ and Aβ 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 Aβ peptides and provides immunohistochemical evidence of Aβ in the human brain and its distribution in the APP/PS1KI and 5XFAD transgenic mouse models.
The Aβ 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 Aβ immunoreactivity. No overt intraneuronal staining was observed.
The findings of this study are consistent with previous reports demonstrating a high aggregation propensity of Aβ peptides and suggest an important role of these N-truncated Aβ species in the process of amyloidogenesis and plaque core formation.
神经毒性淀粉样β（Aβ）肽在脑实质斑块和脑血管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。尽管全长 Aβ 肽（如 Aβ和 Aβ）的存在和影响已被广泛分析，但 N 端截断的 Aβ 肽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 Aβ 肽的新型抗体的产生和特性，并提供了 Aβ 在人脑中的免疫组织化学证据及其在 APP/PS1KI 和 5XFAD 转基因小鼠模型中的分布。
Aβ 染色模式主要局限于 AD 和唐氏综合征病例以及两种 AD 小鼠模型中的淀粉样斑块核心和脑淀粉样血管病。相比之下，弥散性淀粉样沉积物的 Aβ 免疫反应性大多为阴性。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，表明 Aβ 肽具有高聚集倾向，并提示这些 N 端截断的 Aβ 物质在淀粉样变性和斑块核心形成过程中具有重要作用。
