Current and emerging therapeutic approaches in Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline, memory loss, and behavioral changes. AD is characterized by extracellular amyloid-β plaques, intracellular neurofibrillary tau tangles, synaptic loss, neuroinflammation, mitochondrial dysfunction, and altered brain metabolism. AD is clinically divided into early- and late-onset forms. Only a small proportion of early-onset cases are familial and are attributed to mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2). Most cases of AD, whether both early- and late-onset, are sporadic and influenced by a combination of complex genetic, environmental, and age-related factors. Current therapeutic approaches, such as ChEIs and N-Methyl-D-Aspartate (NMDA) antagonists, can help alleviate symptoms. Monoclonal antibodies target amyloid-β42 (Aβ42) and help attenuate amyloid burden in such patients, but their clinical efficacy is limited and remains a topic of debate within the scientific community. Novel approaches (gene and stem cell therapies to nanotechnology, precision medicine and Artificial Intelligence (AI) driven diagnostics and treatments) are under development stage. Implementing early biomarker-based diagnosis in combination with multimodal treatment approaches could fundamentally shift AD management from symptomatic treatment toward disease-modifying strategies. This review aims to provide a critical evaluation of current and emerging therapeutic strategies for AD along with an integrated analysis of outcomes from unsuccessful and successful clinical trials of the emerging therapeutic innovations, highlighting the associated challenges and future treatment perspectives.