A broad review of Tauopathies covering tau isoforms, molecular mechanisms of tau aggregation, neuronal and peripheral organ effects, and cross-talk between tau and other neurodegenerative proteins including alpha-synuclein.

Provides useful synthesis on tau–alpha-synuclein interactions and shared pathogenic pathways that could inform Parkinson's therapeutic target selection or combination strategies, but is primarily conceptual and lacks direct actionable interventions or biomarkers.

A wide range of neurological conditions known as Tauopathies are distinguished by a peculiar accumulation of Tau protein and its effect on the central nervous system (CNS) and beyond. In Tauopathies, Tau aggregation has a primary role in the neurodegenerative process. Clinically, individuals exhibit various symptoms, such as cognitive or behavioural anomalies, mobility issues, memory loss, and language problems. The major Tau isoforms (3R, 4R, or an equal 3R:4R ratio) identified in the inclusion bodies of the brain are used to classify Tauopathies pathologically. We address various Tauopathies, differentiating between primary and secondary forms, the involvement of Tau isoforms, the affected brain areas, and the corresponding neuropathological features. This review emphasizes the pathological and physiological role of Tau protein, providing a comprehensive analysis of the molecular processes enabling Tau aggregation and its subsequent effect on neuronal structure and function. Additionally, the review highlights the complex interactions that exist between Tau and other neurodegenerative proteins, including amyloid-beta in Alzheimer's disease, alpha-synuclein in Parkinson's disease, huntingtin protein in Huntington's disease, and how these relationships worsen Tau pathology and advance neurodegeneration. The organ-specific impact of Tauopathy, including the brain and other peripheral organs, has been discussed. The significance of these findings for future treatment techniques aiming at addressing Tau disease and mitigating its organ-specific repercussions.