Alzheimer's Disease: Current Insights into Risk Factors, Molecular Pathophysiology, Diagnosis, Biomarkers, and Therapeutic Strategies

Abstract

Alzheimer’s disease is the most common cause of dementia and a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and functional disability. In view to increasing their global prevalence, substantial socioeconomic burden, and lack of curative treatment, Alzheimer's disease remains a major public health challenge. This review provides a comprehensive overview of the epidemiology, risk factors, pathophysiology, diagnosis, biomarkers, and current therapeutic strategies for Alzheimer's disease. The disease is influenced by complex interactions among genetic, environmental, vascular, metabolic, and lifestyle-related factors. Major genetic determinants include mutations in APP, PSEN1, and PSEN2, as well as the APOE ε4 allele, while aging remains the strongest non-modifiable risk factor. The pathogenesis of Alzheimer's disease involves amyloid-β accumulation, tau hyperphosphorylation, neurofibrillary tangle formation, synaptic dysfunction, neuroinflammation, oxidative stress, mitochondrial impairment, defective autophagy, blood–brain barrier disruption, and progressive neuronal loss. Advances in diagnosis now integrate clinical and cognitive assessments with neuroimaging and fluid biomarkers, including cerebrospinal fluid, blood, urine, and genetic markers, enabling earlier and more accurate detection. Current management combines symptomatic therapies, including acetylcholinesterase inhibitors and NMDA receptor antagonists, with non-pharmacological interventions such as lifestyle modification, physical activity, dietary optimization, and cognitive training. Recent disease-modifying therapies, particularly anti-amyloid monoclonal antibodies such as lecanemab and donanemab, have demonstrated promising clinical benefits in slowing disease progression. Emerging therapeutic approaches targeting mitochondrial dysfunction, insulin signaling, oxidative stress, autophagy, neuroinflammation, and metabolic pathways may further improve treatment outcomes. Continued research into disease mechanisms, biomarker discovery, and precision medicine is essential for developing more effective diagnostic tools and personalized therapeutic strategies for Alzheimer's disease.