Advances in the drug treatment of Alzheimer's disease: pathophysiology and mechanisms of action.

Abstract

Alzheimer's disease, the leading cause of dementia, is a multifactorial disorder involving amyloid beta (Aβ) and tau deposition, impaired glucose metabolism, neuroinflammation, mitochondrial dysfunction, insulin resistance, and progressive brain atrophy. Anti-Aβ therapies have shown clinical efficacy and are licensed in several countries. Amyloid related imaging abnormalities remain a key safety concern, and reimbursement varies across healthcare systems. The mechanisms underlying continued cognitive decline after Aβ clearance remain unclear and might be independent of amyloid pathology. Because Alzheimer's disease involves multiple pathological processes, effective management will likely require combination treatments addressing tau aggregation, neuroinflammation, synaptic loss, and metabolic dysfunction. Numerous compounds targeting these mechanisms are currently in late stage development for both early and advanced disease. These emerging approaches represent a shift toward multimodal, disease modifying strategies designed to improve patient outcomes and quality of life. Here, we review recent therapeutic advances in Alzheimer's disease and provide perspectives on novel treatment strategies.