The Bidirectional Mechanism of Uric Acid Levels on Alzheimer's Disease: A Narrative Review

Alzheimer's disease (AD) is a central nervous system disorder marked by the extracellular accumulation of β-amyloid (Aβ) plaques in the cerebral cortex and the intracellular aggregation of hyperphosphorylated tau protein, manifesting as progressive cognitive decline and neurodegeneration. The pathological mechanisms of AD are intricate, in clinical treatment, cholinesterase inhibitors have been widely used for many years as symptomatic therapy, alleviating symptoms by improving neurotransmitter levels, but they cannot halt disease progression. Anti-Aβ monoclonal antibodies belong to disease-modifying therapies, although they have achieved breakthrough advances in recent years, strict monitoring requirements must be followed. In recent years, numerous studies have revealed a "U-shaped" association between uric acid (UA) levels and AD risk, along with population heterogeneity. Furthermore, fluctuations in UA levels exert a "bidirectional effect" on AD. At physiological concentrations, UA may confer neuroprotective benefits through antioxidant activity, inhibition of neuroinflammation, preservation of the blood-brain barrier (BBB), regulation of autophagy, and promotion of the clearance of Aβ and tau proteins. Conversely, abnormal UA levels may accelerate AD progression by inducing oxidative stress, activating inflammatory responses, and compromising the BBB. We conducted a comprehensive literature review across multiple medical databases, including PubMed, Embase, Cochrane Library, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI), and Wanfang Data. The selected articles underwent critical evaluation, summarization, and incorporation into this review to highlight research achievements in this domain. This narrative review summarizes current pharmacological treatments for AD and UA, encompassing traditional Chinese medicine (TCM) monomers, compounds, and Western medications. It also thoroughly explores and elucidates the complex mechanism underlying the "bidirectional effect" of UA levels and metabolic pathways on AD, offering insights and theoretical support for future AD drug development.