Abstract

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that remains one of the most significant medical challenges of the 21st century, characterized by relentless cognitive decline, memory impairment, and functional loss. Despite decades of research, effective disease-modifying therapies remain elusive, leaving an urgent need for novel therapeutic strategies. Heparan sulfate (HS), a highly heterogeneous glycosaminoglycan found ubiquitously in the extracellular matrix and on cell surfaces, has emerged as a crucial player in the complex pathophysiology of AD. Its interactions with amyloid-beta (Aβ) peptides promote aggregation and plaque formation, while its binding to hyperphosphorylated tau facilitates neurofibrillary tangle formation, both of which are hallmark features of AD. Additionally, HS modulates neuroinflammatory cascades by influencing microglial activation and cytokine release, further contributing to neuronal damage and disease progression. Beyond its pathogenic roles, HS represents a promising therapeutic target, with potential strategies ranging from synthetic HS mimetics to enzyme inhibitors designed to modulate its activity. In parallel, the integration of Korean Medicines (KM), which has shown efficacy in addressing neuroinflammatory and cognitive disorders through herbal and holistic approaches, offers a unique perspective in the quest for innovative AD treatments. Herbs such as Gastrodia elata and Poria cocos exhibit neuroprotective and anti-inflammatory properties, making them potential candidates for HS-modulating therapies. This review provides a detailed exploration of the biological significance of HS in AD, evaluates emerging therapeutic approaches, and highlights the potential synergy between modern biomedical advancements and the principles of KM. By bridging the gap between traditional knowledge and cutting-edge science, this synthesis lays the groundwork for a transformative, integrative paradigm in AD treatment, aiming to address both the pathological and symptomatic aspects of the disease.