Alzheimer’s Disease: Exploring Pathophysiological Hypotheses and the Role of Machine Learning in Drug Discovery

Abstract

[Abstract]: Alzheimer’s disease (AD) is a major neurodegenerative dementia, with its complex pathophysiology challenging current treatments. Recent advancements have shifted the focus from the traditionally dominant amyloid hypothesis toward a multifactorial understanding of the disease. Emerging evidence suggests that while amyloid-beta (A𝛽�) accumulation is central to AD, it may not be the primary driver but rather part of a broader pathogenic process. Novel hypotheses have been proposed, including the role of tau protein abnormalities, mitochondrial dysfunction, and chronic neuroinflammation. Additionally, the gut–brain axis and epigenetic modifications have gained attention as potential contributors to AD progression. The limitations of existing therapies underscore the need for innovative strategies. This study explores the integration of machine learning (ML) in drug discovery to accelerate the identification of novel targets and drug candidates. ML offers the ability to navigate AD’s complexity, enabling rapid analysis of extensive datasets and optimizing clinical trial design. The synergy between these themes presents a promising future for more effective AD treatments.