The association of the Wnt/β-catenin signaling pathway with Alzheimer's disease

With the global rise in population aging, the incidence of Alzheimer's disease (AD) continues to increase, posing a substantial burden on individuals, families, and healthcare systems. However, at present, the drugs approved by FDA for treating AD can only relieve symptoms, but cannot cure or reverse the disease. Therefore, it is urgent to study the signal pathways related to AD and the drugs to improve the pathological changes of AD.The Wnt/β-catenin signaling pathway, known for its functional diversity, evolutionary conservation, and relevance to multiple diseases, holds a pivotal role in both basic research and therapeutic development. This pathway is essential for regulating critical biological processes, including embryonic development, tissue homeostasis, cell proliferation, differentiation, and apoptosis.In AD, downregulation of the Wnt/β-catenin signaling pathway has been implicated in key pathological features, such as tau hyperphosphorylation, amyloid-β (Aβ) accumulation, neuronal degeneration, synaptic loss, cognitive impairment, oxidative stress, mitochondrial dysfunction, blood-brain barrier disruption, and neuroinflammation. This review comprehensively discusses the deregulation of the Wnt/β-catenin pathway in AD and how it contributes to disease progression. Furthermore, we highlighted emerging pharmacological activators of this pathway exhibiting potential as therapeutic agents for AD.