Advances in Alzheimer's disease: mechanistic insights and therapeutic targets

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline, memory loss, and behavioral disturbances, eventually leading to dementia and severely diminishing quality of life. With the global population aging, AD has become an unprecedented challenge for society and families. Recent advances in the development of amyloid-beta (Aβ)-targeting monoclonal anti-bodies, like lecanemab and donanemab, provided hope for slowing or even halting disease progression. However, these treatments have not yet achieved the ultimate goal of reversing cognitive deterioration and restoring normal function. The complexity of AD stems from multiple contributing factors, with Aβ deposition and tau protein tangles being central to its pathology, while genetic predispositions, aging, and systemic factors further drive disease progression. Addressing AD by targeting a single factor has proven insufficient, highlighting the need for a comprehensive understanding of its multifaceted mechanisms. This review explores the latest advances in AD mechanistic research and therapeutic development, focusing on key areas such as amyloid precursor protein (APP) metabolism, Aβ dynamics, Aβ antibody immunotherapy, tau protein dysfunction, genetic influences, aging mechanisms, and systemic factors. By critically examining these aspects, we aim to provide insights that support more holistic approaches to AD diagnosis and treatment, ultimately laying the groundwork for innovative strategies to combat this debilitating disease.