零星的阿尔茨海默病和癌症在流行病学上保持着相反的相互关系，探索两者之间的逆向发病机制对我们理解两种疾病都至关重要。阿尔茨海默病（AD）中的认知功能障碍可能是由于大脑中适应性储备物的耗竭所致。大脑能量储存有限，并通过神经血管和神经代谢耦合进行动态调节。神经退行性疾病的研究一直被神经中心主义观点主导，即神经细胞缺陷导致了这些疾病。然而，在AD中提出的二重打击血管学说使我们开始关注血管系统的改变，尤其是低灌注。慢性缺氧是AD和癌症共享的特征。有趣的是，慢性缺氧对癌症和AD产生了相互矛盾的影响。在本文中，我们讨论了这两种疾病发病机理之间的潜在联系，从相似的上游环境到截然相反的下游效应。我们提出相反的潜在机制，包括缺氧诱导因子-1α的上调和下调，Warburg效应和反Warburg效应，乳酸介导的细胞内酸性和碱性条件，以及VDAC1介导的凋亡和抗凋亡，并寻找可能被确定为癌症和AD之间交汇点的调节因子。版权所有 © 2023作者。Elsevier Inc.保留所有权利。

Sporadic Alzheimer's disease and cancer remain epidemiologically inversely related, and exploring the reverse pathogenesis is important for our understanding of both. Cognitive dysfunctions in Alzheimer's disease (AD) might result from the depletion of adaptive reserves in the brain. Energy storage in the brain is limited and is dynamically regulated by neurovascular and neurometabolic coupling. The research on neurodegenerative diseases has been dominated by the neurocentric view that neuronal defects cause the diseases. However, the proposal of the 2-hit vascular hypothesis in AD led us to focus on alterations in the vasculature, especially hypoperfusion. Chronic hypoxia is a feature shared by AD and cancer. It is interesting how contradicting chronic hypoxia's effects on both cancer and AD are. In this article, we discuss the potential links between the 2 diseases' etiology, from comparable upstream circumstances to diametrically opposed downstream effects. We suggest opposing potential mechanisms, including upregulation and downregulation of hypoxia-inducible factor-1α, the Warburg and reverse-Warburg effects, lactate-mediated intracellular acidic and alkaline conditions, and VDAC1-mediated apoptosis and antiapoptosis, and search for regulators that may be identified as the crossroads between cancer and AD.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.