Alzheimer’s disease (AD) is pathologically defined by the presence of fibrillar amyloid β (Aβ) peptide in extracellular senile plaques and tau filaments in intracellular neurofibrillary tangles. Extensive research has focused on understanding the assembly mechanisms and neurotoxic effects of Aβ during the last decades but still we only have a brief understanding of the disease associated biological processes. This review highlights the many other constituents that, beside Aβ, are accumulated in the plaques, with the focus on extracellular proteins. All living organisms rely on a delicate network of protein functionality. Deposition of significant amounts of certain proteins in insoluble inclusions will unquestionably lead to disturbances in the network, which may contribute to AD and copathology. This paper provide a comprehensive overview of extracellular proteins that have been shown to interact with Aβ and a discussion of their potential roles in AD pathology. Methods that can expand the knowledge about how the proteins are incorporated in plaques are described. Top-down methods to analyze post-mortem tissue and bottom-up approaches with the potential to provide molecular insights on the organization of plaque-like particles are compared. Finally, a network analysis of Aβ-interacting partners with enriched functional and structural key words is presented.

中文翻译：

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淀粉样蛋白斑的细胞外蛋白成分及其在阿尔茨海默病病理学中的作用

阿尔茨海默病 (AD) 的病理学定义是细胞外老年斑中存在纤维状淀粉样蛋白 β (Aβ) 肽，细胞内神经原纤维缠结中存在 tau 丝。过去几十年来，广泛的研究集中在了解 Aβ 的组装机制和神经毒性作用，但我们对疾病相关的生物过程仍然只有简要的了解。这篇综述强调了除 Aβ 之外，斑块中积累的许多其他成分，重点是细胞外蛋白。所有生物体都依赖于蛋白质功能的微妙网络。大量的某些蛋白质沉积在不溶性内含物中无疑会导致网络紊乱，这可能会导致 AD 和共病理。本文全面概述了已被证明与 Aβ 相互作用的细胞外蛋白，并讨论了它们在 AD 病理学中的潜在作用。描述了可以扩展有关蛋白质如何掺入斑块的知识的方法。比较了分析死后组织的自上而下的方法和有可能提供有关斑块状颗粒组织的分子见解的自下而上的方法。最后，提出了具有丰富功能和结构关键词的 Aβ 相互作用伙伴的网络分析。