The involvement of Na,K-ATPase enzyme in the development of Alzheimer's disease

The sodium‑potassium pump (Na,K-ATPase) is an essential membrane-bound enzyme that maintains electrochemical gradients across the plasma membrane in animal cells. Growing evidence implicates its dysfunction in the pathogenesis of Alzheimer's disease (AD). This review summarizes findings from studies utilizing postmortem human brain tissue, rodent models of AD, and in vitro systems to explore the role of Na,K-ATPase in AD and the potential for its modulation by naturally occurring compounds. The link between Na,K-ATPase and AD can be explained through several mechanisms. First, the enzyme may serve as a downstream target of oxidative stress, a well-known hallmark of AD. Second, amyloid-beta (Aβ) peptides bind to Na,K-ATPase even under normal physiological conditions; however, in AD, where Aβ levels are abnormally elevated, this interaction may impair enzyme activity. Third, Na,K-ATPase contributes to cerebrospinal fluid dynamics, potentially influencing Aβ clearance from the brain. A larger body of evidence supports the involvement of Na,K-ATPase in AD progression, though inconsistencies in the literature likely reflect differences in experimental models and methodologies. Importantly, Na,K-ATPase activity also shows promise as a biomarker for assessing AD risk or progression, particularly in readily accessible biological materials such as blood. In addition, naturally occurring antioxidants from fruits, vegetables, and medicinal plants have been shown to protect Na,K-ATPase activity, suggesting a potential therapeutic strategy to slow or mitigate cognitive decline associated with AD.