Benefits, Pitfalls, and Alternatives to Amyloid-Targeting Alzheimer's Disease Drugs

Abstract

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that leads to a gradual decline in cognitive functions. This condition is primarily characterized by the accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles in the brain, which disrupt neuronal communication and contribute to cognitive impairment. The aggregation of Aβ into plaques is one of the main hallmarks of AD pathology, and understanding this process is crucial for developing effective treatments.  Recently, three drugs were approved by the FDA: aducanumab, donanemab, and lecanemab. These drugs target Aβ plaques, aiming to reduce plaque accumulation and help alleviate symptoms. While these treatments represent significant progress, challenges remain in addressing the underlying mechanisms of the disease. In addition to targeting Aβ, there is growing interest in the role of microglia—the brain's immune cells—in the pathology of AD. Microglia play a critical role in clearing amyloid plaques and maintaining brain health. Controlling microglial activity may offer a novel therapeutic approach. This paper aims to provide an overview of the recently approved drugs, evaluate their efficacy and safety, and explore the potential of targeting microglia as a complementary strategy in AD treatment. Through this discussion, we hope to shed light on the evolving landscape of AD treatment and the importance of a multifaceted approach to combating this complex condition.