Oxygen metabolism abnormality plays a crucial role in the pathogenesis of Alzheimer's disease (AD) via several mechanisms, including hypoxia, oxidative stress, and mitochondrial dysfunction. Hypoxia condition usually results from living in a high-altitude habitat, cardiovascular and cerebrovascular diseases, and chronic obstructive sleep apnea. Chronic hypoxia has been identified as a significant risk factor for AD, showing an aggravation of various pathological components of AD, such as amyloid β-protein (Aβ) metabolism, tau phosphorylation, mitochondrial dysfunction, and neuroinflammation. It is known that hypoxia and excessive hyperoxia can both result in oxidative stress and mitochondrial dysfunction. Oxidative stress and mitochondrial dysfunction can increase Aβ and tau phosphorylation, and Aβ and tau proteins can lead to redox imbalance, thus forming a vicious cycle and exacerbating AD pathology. Hyperbaric oxygen therapy (HBOT) is a non-invasive intervention known for its capacity to significantly enhance cerebral oxygenation levels, which can significantly attenuate Aβ aggregation, tau phosphorylation, and neuroinflammation. However, further investigation is imperative to determine the optimal oxygen pressure, duration of exposure, and frequency of HBOT sessions. In this review, we explore the prospects of oxygen metabolism in AD, with the aim of enhancing our understanding of the underlying molecular mechanisms in AD. Current research aimed at attenuating abnormalities in oxygen metabolism holds promise for providing novel therapeutic approaches for AD.
Keywords: Alzheimer's disease; HIF-1; Hypoxia; Mitochondrial dysfunction; Oxidative stress; Oxygen metabolism.
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