The pathophysiology of Alzheimer's disease (AD) remains to be elucidated. The amyloid hypothesis holds explanatory power but has limitations. This article suggests that amyloid deposition and increased permeability of the blood–brain barrier are independent early events in the disease process, which together fashion a distinct microglial activation phenotype. Downstream events including, phagocytosis of synapses and persistent glutamate signaling through N-methyl-D-aspartate receptors drive neurodegeneration and tau pathology. This hypothesis draws on several strands of evidence and aims to illuminate several of the unexplained temporal and spatial features of AD.

中文翻译：

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假设：阿尔茨海默病中小胶质细胞表型的调节驱动神经变性

阿尔茨海默病 (AD) 的病理生理学仍有待阐明。淀粉样蛋白假说具有解释力，但也有局限性。这篇文章表明，淀粉样蛋白沉积和血脑屏障通透性增加是疾病过程中独立的早期事件，它们共同形成了独特的小胶质细胞激活表型。下游事件包括突触的吞噬作用和通过 N-甲基-D-天冬氨酸受体的持久性谷氨酸信号传导驱动神经变性和 tau 病理。该假设借鉴了多条证据，旨在阐明 AD 的几个无法解释的时间和空间特征。