Emerging therapeutic targets beyond amyloid and tau in Alzheimer's Disease: Implications for lifestyle, metabolism and preventive medicine.

Abstract

Alzheimer's disease (AD) is the leading cause of dementia and remains a major global health challenge. Although current disease-modifying therapies primarily target amyloid-β and tau pathology, their clinical efficacy is limited. Increasing evidence indicates that AD is a multifactorial disorder involving neuroinflammation, mitochondrial dysfunction, impaired autophagy-lysosomal pathways, and dysregulated lipid metabolism. These interconnected mechanisms contribute to disease progression and represent promising therapeutic targets. This narrative review summarizes current evidence on emerging treatment strategies beyond the classical amyloid and tau paradigm, with particular emphasis on microglial activation, mitochondrial function, autophagy, and lipid homeostasis. Additionally, the translational potential of lifestyle-based interventions, including physical activity and metabolic regulation, is discussed. A broader understanding of AD pathogenesis may support the development of integrated therapeutic approaches combining pharmacological and non-pharmacological strategies to improve clinical outcomes.