Alzheimer's disease (AD) is a progressive neurodegenerative disorder that results from the accumulation of plaques by cleaved Aβ42 peptides as well as neurofibrillary tangles of tau proteins. This accumulation triggers a complex cascade of cytotoxic, neuroinflammatory, and oxidative stresses that lead to neuronal death throughout the progression of the disease. Much of research in AD focused on the 2 pathologic proteins. Interestingly, another form of dementia with similar clinical manifestations of AD, but preferentially affected much older individuals, was termed as limbic-predominant age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy (LATE) and involved the cytotoxic intraneuronal deposition of phosphorylated TDP-43. TDP-43 proteinopathy was also found to be involved in AD pathology leading to the possibility that AD and LATE may share a common upstream etiology. This paper discusses the roles molecular pathways known in AD may have on influencing TDP-43 proteinopathy and the development of AD, LATE, or the 2 being comorbid with each other.

中文翻译：

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Aβ 依赖和独立通路对阿尔茨海默病中 TDP-43 蛋白病的影响：与 LATE-NC 的可能联系

阿尔茨海默病 (AD) 是一种进行性神经退行性疾病，由裂解的 Aβ42 肽以及 tau 蛋白的神经原纤维缠结引起的斑块积聚所致。这种积累引发了细胞毒性、神经炎症和氧化应激的复杂级联反应，在整个疾病进展过程中导致神经元死亡。AD 的大部分研究都集中在 2 种病理蛋白上。有趣的是，另一种痴呆症与 AD 的临床表现相似，但优先影响年龄更大的个体，被称为边缘主导型年龄相关交互反应 DNA 结合蛋白 43 (TDP-43) 脑病 (LATE)，并涉及细胞毒性内神经元磷酸化 TDP-43 的沉积。还发现 TDP-43 蛋白病与 AD 病理学有关，导致 AD 和 LATE 可能具有共同的上游病因。本文讨论了 AD 中已知的分子通路在影响 TDP-43 蛋白病和 AD、LATE 或两者合并症的发展方面可能发挥的作用。