According to its higher prevalence worldwide among all dementia cases, Alzheimer's disease (AD) is placed as the first pathology affecting people aged of more than 65 years old. Since it first description in 1907, profound research and groundbreaking observations have been made concerning the histopathological and molecular aspects of its associated neurodegeneration. However, the molecular mechanisms of AD pathogenesis and progression remain still poorly understood. In addition, an efficient therapeutic approach to either prevent or stop the disease progression has not yet been developed. It becomes hence crucial to develop research in emerging areas raising from groundbreaking concepts and supported by new mechanistic approaches in order to unveil novel aspects of the physiopathology of neurodegeneration and therefore design new therapeutic approaches to treat these pathologies.The present study is focused on the role of heparan sulfate (HS), a particular member of the glycosaminoglycan family, in the physiopathology of neurodegenerative disorders, such as AD and related dementias, termed tauopathies. Based on numerous separate observations suggesting an association between tau pathology characteristic of tauopathies and HS, this research explores the pathological implications of such interaction by the means of molecular, cellular, and animal studies. As a result, I hereby present evidence suggesting a crucial involvement of HS in tau pathological events, such as abnormal phosphorylation, inclusion formation, and assembly propagation.Globally, the present work unveils a strong implication of highly sulfated HS in tau pathology associated to AD and related tauopathies, and opens a wide array of novel research pathways to deepen into the characterization of tau /HS interplay and its pathophysiologic consequences. In addition, it suggests alternative pharmacological targets that could bring some hope in finding an effective treatment for AD.