TDP-43 Proteinopathy and Tauopathy: Do They Have Pathomechanistic Links?

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Abstract

Transactivation response DNA binding protein 43 kDa (TDP-43) and tau are major pathological proteins of neurodegenerative disorders, of which neuronal and glial aggregates are pathological hallmarks. Interestingly, accumulating evidence from neuropathological studies has shown that comorbid TDP-43 pathology is observed in a subset of patients with tauopathies, and vice versa. The concomitant pathology often spreads in a disease-specific manner and has morphological characteristics in each primary disorder. The findings from translational studies have suggested that comorbid TDP-43 or tau pathology has clinical impacts and that the comorbid pathology is not a bystander, but a part of the disease process. Shared genetic risk factors or molecular abnormalities between TDP-43 proteinopathies and tauopathies, and direct interactions between TDP-43 and tau aggregates, have been reported. Further investigations to clarify the pathogenetic factors that are shared by a broad spectrum of neurodegenerative disorders will establish key therapeutic targets.

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Riku, Y., Yoshida, M., Iwasaki, Y., Sobue, G., Katsuno, M., & Ishigaki, S. (2022, December 1). TDP-43 Proteinopathy and Tauopathy: Do They Have Pathomechanistic Links? International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms232415755

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