ALZHEIMER’S TODAY: THE BREAKTHROUGHS AND HURDLES IN MANAGING THE DISEASE

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and leading cause of dementia, imposing a rapidly growing clinical and socioeconomic burden worldwide. This narrative review summarizes current understanding of AD pathophysiology, advances in diagnostics, and emerging therapeutic approaches. Hallmark mechanisms include amyloid-β plaque deposition, tau hyperphosphorylation, mitochondrial dysfunction, oxidative stress, glutamatergic excitotoxicity, metal dyshomeostasis and defective autophagy, all converging on synaptic failure and neuronal loss. The 2018 NIA–AA ATN (amyloid, tau, neurodegeneration) framework has shifted diagnosis toward a biomarker-based, biological definition of AD, incorporating CSF, PET, MRI and novel blood, saliva and tear biomarkers, as well as microRNA signatures for earlier detection across the preclinical–MCI–dementia continuum. Symptomatic therapies with acetylcholinesterase inhibitors and the NMDA antagonist memantine remain standard of care, while monoclonal antibodies such as aducanumab and lecanemab represent first-generation disease-modifying agents but raise concerns regarding amyloid-related imaging abnormalities and cost. Ongoing trials of biologics and small molecules targeting amyloid, tau, inflammation, oxidative stress and neuroprotection highlight a transition toward precision, multi-targeted strategies. Continued research into accessible biomarkers, safer long-acting formulations and adherence-enhancing approaches is essential to reduce the future global burden of AD.