Alzheimer's disease (AD) is a neurodegenerative disorder associated with continual decline in cognition and ability to perform routine functions such as remembering familiar places or understanding speech. For decades, amyloid beta (Aβ) was viewed as the driver of AD, triggering neurodegenerative processes such as inflammation and formation of neurofibrillary tangles (NFTs). This approach has not yielded therapeutics that cure the disease or significant improvements in long-term cognition through removal of plaques and Aβ oligomers. Some researchers propose alternate mechanisms that drive AD or act in conjunction with amyloid to promote neurodegeneration. This review summarizes the status of AD research and examines research directions including and beyond Aβ, such as tau, inflammation, and protein clearance mechanisms. The effect of aging on microvasculature is highlighted, including its contribution to reduced blood flow that impairs cognition. Microvascular alterations observed in AD are outlined, emphasizing imaging studies of capillary malfunction. The review concludes with a discussion of two therapies to protect tissue without directly targeting Aβ for removal: (1) administration of growth factors to promote vascular recovery in AD; (2) inhibiting activity of a calcium-permeable ion channels to reduce microglial activation and restore cerebral vascular function.

阿尔茨海默氏病（AD）是一种神经退行性疾病，与认知能力持续下降和执行常规功能（例如记住熟悉的地方或理解语音）的能力有关。数十年来，淀粉样蛋白（Aβ）被视为AD的驱动器，引发了神经退行性过程，例如炎症和神经原纤维缠结（NFT）的形成。通过去除斑块和Aβ寡聚体，该方法尚未产生治愈疾病的疗法或长期认知的显着改善。一些研究人员提出了替代机制来驱动AD或与淀粉样蛋白共同促进神经变性。这篇综述总结了AD研究的现状，并研究了包括Aτ在内的研究方向，例如tau，炎症和蛋白质清除机制。着重指出了衰老对微脉管系统的影响，包括其对减少血流，损害认知的作用。概述了在AD中观察到的微血管改变，强调了对毛细血管功能障碍的影像学研究。该综述以讨论两种在不直接靶向Aβ的情况下保护组织的疗法为结束：（1）给予生长因子以促进AD的血管恢复；（2）抑制钙可渗透离子通道的活性，以减少小胶质细胞的活化并恢复脑血管功能。该综述以讨论两种在不直接靶向Aβ的情况下保护组织的疗法为结束：（1）给予生长因子以促进AD的血管恢复；（2）抑制钙可渗透离子通道的活性，以减少小胶质细胞的活化并恢复脑血管功能。该综述以讨论两种在不直接靶向Aβ的情况下保护组织的疗法为结束：（1）给予生长因子以促进AD的血管恢复；（2）抑制钙可渗透离子通道的活性，以减少小胶质细胞的活化并恢复脑血管功能。