Category: Parkinsonism, Atypical: PSP, CBD
Objective: This study monitored the formation of CBD (corticobasal degeneration)-type fibrils that exhibit astrocytic plaques, a characteristic CBD pathology, using Legumain-cleavage site-specific antibodies and CBD-specific biochemical properties.
Background: Corticobasal degeneration (CBD) is a major four-repeat tauopathy along with progressive supranuclear palsy (PSP).The detergent-insoluble 37-40-kDa C-terminal tau fragments (CTFs) of CBD are considered to have a biochemical diagnostic value. However, it remains to be clarified which protease generates disease-specific CTFs.
Method: We generated antibodies that specifically recognize the N-terminal end of CTFs. Using these antibodies, biochemical analysis and immunohistochemistry were performed with autopsied brains of CBD, PSP, Alzheimer’s disease (AD), and controls without neurodegenerative diseases along with cultured cells and mice seeded with tau fibrils.
Results: While AD- and PSP-type tau fibrils at N167 and N368 were cleaved by the lysosomal protease legumain (LGMN), CBD-type fibrils were resistant to the LGMN cleavage at N368, resulting in the generation of CBD-type CTFs. The cleavage property of LGMN on CBD-type tau fibrils was also observed in tau fibrils amplified in cultured cells and mice using tau seeds from CBD patients. The resistance of LGMN cleavage in CBD-type tau fibrils was lost by denaturing tau fibrils, indicating that the CBD-specific cleavage pattern is due to the CBD-specific tau fibril fold. Consistent with the above biochemical observation, astrocytic plaques in CBD were negative with anti-tau N368 cleavage site-specific antibody, while tufted astrocytes in PSP were positive.
Conclusion: Our study using tau fragment-specific antibodies supports the presence of CBD-specific tau fibril folds. It would contribute to developing novel pathological diagnoses for tauopathy-associated neurodegenerative diseases.
To cite this abstract in AMA style:
D. Taniguchi, T. Hatano, Y. Imai, N. Hattori. Legmain/Asparaginyl endopeptidase-resistant tau fibril fold produces corticobasal degeneration-specific C-terminal tau fragment [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/legmain-asparaginyl-endopeptidase-resistant-tau-fibril-fold-produces-corticobasal-degeneration-specific-c-terminal-tau-fragment/. Accessed October 12, 2024.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/legmain-asparaginyl-endopeptidase-resistant-tau-fibril-fold-produces-corticobasal-degeneration-specific-c-terminal-tau-fragment/