The Impact of Air Pollution and Obesity on Cognitive Decline and Risk of Alzheimer's Disease.

Obesity and air pollution are two pervasive and increasingly prevalent risk factors for neurodegenerative diseases, like Alzheimer's disease. Both independently disrupt brain homeostasis through overlapping mechanisms, including chronic neuroinflammation, oxidative stress, and insulin resistance. Recent evidence highlights the Wnt/β-catenin signaling pathway as a critical integrator of these insults, mediating neuroprotective processes such as synaptic plasticity, blood-brain barrier integrity, and neuronal survival. In this review, we synthesize emerging data on how obesity-driven metabolic dysfunction and air pollution-induced oxidative injury synergize to impair brain metabolism and accelerate cognitive decline. We describe the roles of pathways such as JAK-STAT, NF-κB, and TLR4 signaling cascades, as well as leptin and adiponectin imbalances, in modulating glial reactivity and neuroimmune signaling. Particular attention is given to the suppression of Wnt/β-catenin signaling in obese and pollution-exposed brains, and its consequences for Alzheimer's disease pathology, including β-amyloid accumulation and tau hyperphosphorylation. Finally, we examine the translational implications, highlighting the Wnt pathway as a potential therapeutic target that offers neuroprotection in the context of dual metabolic and environmental stress. Together, these insights provide a mechanistic framework that links systemic dysfunction to central nervous system vulnerability, offering pathways for intervention in at-risk populations.