Beneficial and Detrimental Effects of Uric Acid on Alzheimer's Disease.

Abstract

The interconnection between brain function and hyperuricemia remains controversial since the available evidence indicates both the potent neuroprotective role of uric and its negative cardiovascular and metabolic effects, possible prooxidant activity. A mixed (protective and risk) effect of uric acid on neurological disorders was assumed. Among the neurodegenerative diseases, Alzheimer's disease remains the most prevalent, causes disability, and lacks highly effective treatments. Therefore, this review aims to delineate the beneficial and detrimental effects of uric acid on Alzheimer's disease. This can not only facilitate estimating the benefits and risks of urate-lowering or urate-increasing interventions in different conditions but also can enhance understanding of the molecular pathways associated with the protective role of uric acid, leading to the identification of new therapeutic targets for neuroprotection. Firstly, we addressed interconnections between UA and AD in different patients and population subgroups. Secondly, we analysed which differences can arise at the level of uric acid transport to the brain, its influence on BBB, and its presence in brain tissue and cerebrospinal fluid. Such aspects as xanthine oxidase interrelationship with the risk of cognitive impairment was elucidated, as well as the unexpected interconnection between uric acid exchange and the cholinergic system. Finally, an analysis was done of the beneficial and detrimental effects of uric acid on such targets of Alzheimer's disease pathogenesis as the amyloid-β pathway, proinflammatory markers, peroxynitrite scavenging, and other aspects of prooxidant-antioxidant status.