Tau biomarkers for neurodegenerative diseases: Current state and perspectives

Neurodegenerative diseases, particularly tauopathies, pose significant global health challenges, especially in aging populations. Tauopathies are characterized by progressive neuronal damage and intracellular deposits of hyperphosphorylated tau. Early and accurate diagnosis is hindered by overlapping clinical features and reliance on post-mortem analyses, emphasizing the need for reliable in vivo biomarkers to improve early diagnosis and management. Advances in tau biomarkers and imaging have facilitated targeted Alzheimer's disease therapies, but progress for other tauopathies remains inadequate. Future diagnostic frameworks should integrate multiple biomarkers across different tissues within specific timelines. However, challenges such as co-pathologies and limited understanding of pathogenic mechanisms remain significant obstacles. Emerging ultrasensitive technologies, including seeding amplification assays and minimally invasive sources of biomarkers like skin biopsy, hold promise for biomarker discovery. Here, we present the current clinical classification of tau proteinopathies, the challenges that are posed by the actual diagnostic criteria, followed by the most recent advancements in tau biomarker technologies.