Can understanding the molecular basis of tauopathies unlock new therapies for Alzheimer's disease? This comprehensive review delves into the intricate relationship between tau protein abnormalities and neurodegenerative disorders, highlighting recent advancements in understanding the etiology and pathogenesis of these devastating conditions. The paper explores the defining neuropathological characteristics of Alzheimer's disease, including the presence of filamentous tau lesions and fibrillar amyloid β peptides. Furthermore, it examines neurodegenerative tauopathies such as corticobasal degeneration, progressive supranuclear palsy, and Pick's disease, as well as hereditary frontotemporal dementia. Multiple tau gene mutations are identified as pathogenic factors, with tau polymorphisms acting as genetic risk indicators for sporadic progressive supranuclear palsy and corticobasal degeneration. Emerging data supports the hypothesis that different tau gene mutations impair tau functions, promote tau fibrillization, or disrupt tau gene splicing, thereby leading to the formation of biochemically and structurally distinct tau aggregates. The study emphasizes the need to test hypothetical mechanisms through transgenic models to accelerate the discovery of more effective therapies for neurodegenerative tauopathies and related disorders, including Alzheimer's disease. While diverse FTDP-17 syndromes exist, influenced by genetic or epigenetic factors, the insights gained from transgenic models promise to unveil more effective therapies for neurodegenerative tauopathies, including Alzheimer's disease, by targeting the pathogenic mechanisms of tau abnormalities.
Published in the Annual Review of Neuroscience, this paper aligns with the journal's focus on providing comprehensive reviews of significant advances in the field. By examining the molecular underpinnings of neurodegenerative diseases, specifically the role of tau protein, the paper contributes to the journal's exploration of brain function and dysfunction. Its extensive citation of related works in neuroscience underscores its relevance to the journal's readership and its contribution to the ongoing scientific dialogue.