To promote new thinking of the pathogenesis of Alzheimer's disease (AD), we examine the central role of mitochondrial dysfunction in AD. Pathologically, AD is characterized by progressive neuronal loss and biochemical abnormalities including mitochondrial dysfunction. Conventional thinking has dictated that AD is driven by amyloid beta pathology, per the Amyloid Cascade Hypothesis. However, the underlying mechanism of how amyloid beta leads to cognitive decline remains unclear. A model correctly identifying the pathogenesis of AD is critical and needed for the development of effective therapeutics. Mitochondrial dysfunction is closely linked to the core pathological feature of AD: neuronal dysfunction. Targeting mitochondria and associated proteins may hold promise for new strategies for the development of disease-modifying therapies. According to the Mitochondrial Cascade Hypothesis, mitochondrial dysfunction drives the pathogenesis of AD, as baseline mitochondrial function and mitochondrial change rates influence the progression of cognitive decline.

中文翻译：

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线粒体功能障碍在阿尔茨海默病发病机制中的作用

为了促进对阿尔茨海默病 (AD) 发病机制的新思考，我们研究了线粒体功能障碍在 AD 中的核心作用。在病理学上，AD 的特征是进行性神经元丢失和生化异常，包括线粒体功能障碍。根据淀粉样蛋白级联假说，传统思维认为 AD 是由淀粉样蛋白 β 病理学驱动的。然而，β 淀粉样蛋白如何导致认知能力下降的潜在机制仍不清楚。正确识别 AD 发病机制的模型对于开发有效的治疗方法至关重要和需要。线粒体功能障碍与AD的核心病理特征密切相关：神经元功能障碍。靶向线粒体和相关蛋白可能为开发疾病缓解疗法的新策略带来希望。