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- Title
Generation and characterization of monoclonal antibodies against pathologically phosphorylated TDP-43.
- Authors
Castellanos Otero, Paula; Todd, Tiffany W.; Shao, Wei; Jones, Caroline J.; Huang, Kexin; Daughrity, Lillian M.; Yue, Mei; Sheth, Udit; Gendron, Tania F.; Prudencio, Mercedes; Oskarsson, Björn; Dickson, Dennis W.; Petrucelli, Leonard; Zhang, Yong-Jie
- Abstract
Inclusions containing TAR DNA binding protein 43 (TDP-43) are a pathological hallmark of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). One of the disease-specific features of TDP-43 inclusions is the aberrant phosphorylation of TDP-43 at serines 409/410 (pS409/410). Here, we developed rabbit monoclonal antibodies (mAbs) that specifically detect pS409/410-TDP-43 in multiple model systems and FTD/ALS patient samples. Specifically, we identified three mAbs (26H10, 2E9 and 23A1) from spleen B cell clones that exhibit high specificity and sensitivity to pS409/410-TDP-43 peptides in an ELISA assay. Biochemical analyses revealed that pS409/410 of recombinant TDP-43 and of exogenous 25 kDa TDP-43 C-terminal fragments in cultured HEK293T cells are detected by all three mAbs. Moreover, the mAbs detect pS409/410-positive TDP-43 inclusions in the brains of FTD/ALS patients and mouse models of TDP-43 proteinopathy by immunohistochemistry. Our findings indicate that these mAbs are a valuable resource for investigating TDP-43 pathology both in vitro and in vivo.
- Subjects
MONOCLONAL antibodies; DNA-binding proteins; FRONTOTEMPORAL dementia; B cells; AMYOTROPHIC lateral sclerosis
- Publication
PLoS ONE, 2024, Vol 19, Issue 4, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0298080