TITLE:
Alzheimer’s Disease Pharmacotherapy: The Potential for Drug Repurposing
AUTHORS:
Aniqa Niha, Zvi G. Loewy
KEYWORDS:
Alzheimer’s Disease, Neurodegeneration, β-Amyloid, Tau Protein, Drug Repurposing, PAI-1, Biomarkers
JOURNAL NAME:
Neuroscience and Medicine,
Vol.16 No.4,
December
23,
2025
ABSTRACT: Background: Alzheimer’s Disease (AD) is characterized by neurodegeneration affecting behavioral and cognitive function including memory, comprehension, language, attention, reasoning, and judgment. As the most prevalent forms of dementia, AD comprises approximately two-thirds of cases involving individuals 65 and older. The pathogenesis of AD is multifactorial-encompassing β-amyloid plaque accumulation, tau neurofibrillary tangles, neurotransmitter imbalances, neuroinflammation, and other causative factors such as oxidative stress and gut dysbiosis. Objective: This review aims to explore the emerging approach of drug repurposing by utilizing current FDA-approved drugs for new therapeutic indications. Methods: A comprehensive literature review using trusted databases such as PubMed, MEDLINE, EMBASE, and relevant internet sources from 1997 to 2025 was conducted. Relevant search terms included “Alzheimer’s pathology,” “PAI-1 and Alzheimer’s,” “current AD therapies,” and “drug repurposing.” The selection of studies was conducted based on relevance, quality, and clinical significance, and was independently reviewed by two investigators. Results: Current treatments for AD only offer symptomatic relief via the modulation of target neurotransmitters and amyloid pathology. Monoclonal antibodies, tau-targeting agents, and neuroprotective compounds are novel investigational agents that are of interest due to their disease-modifying properties. The process of drug repurposing through mechanism-based, computational, and epidemiologic strategies, is a promising tool that has identified candidates like metformin, pioglitazone, statins, and antihypertensives for the treatment of AD. Plasminogen Activator Inhibitor-1 (PAI-1) inhibitory drugs have also emerged as candidates of interest due to involvement in AD-related fibrinolytic and inflammatory pathways. Conclusion: Effective disease-modifying treatments remain limited despite significant progress in AD research over the years. Acceleration of therapeutic development can be facilitated by repurposing existing drugs, especially when this approach is combined with biomarker profiling, computational modeling, and systems biology techniques. Further research into targets such as PAI-1 may lead to breakthroughs in halting or reversing AD progression.