Vol. 10, Issue 11, Part D (2024)

Abstract
Alzheimer's disease (AD) is the most common cause of dementia, affecting millions of individuals worldwide. The hallmark of AD pathology is the accumulation of amyloid-beta (Aβ) plaques in the brain, which triggers a cascade of events leading to synaptic dysfunction, neuronal loss, and cognitive impairment. Understanding the role of amyloid in AD pathogenesis has driven extensive research aimed at developing therapeutic interventions that target the amyloid pathway. Therapeutic strategies include inhibiting the production of Aβ, preventing its aggregation, and promoting its clearance from the brain. This comprehensive review examines both preclinical studies using animal models and clinical trials in human populations that explore various novel compounds aimed at the amyloid pathway. Emphasis is placed on the mechanisms of action of these compounds, such as BACE1 and γ-secretase inhibitors, monoclonal antibodies, and immunotherapies. Despite promising preclinical results, clinical trials have often faced challenges, including lack of efficacy in cognitive improvement, adverse side effects, and the complexity of AD pathology. This review analyzes these challenges and offers insights into the potential future directions for amyloid-targeting therapies in AD, with a focus on the importance of early intervention and multi-targeted approaches to achieve clinical success.