biostudies-literatureUnknown12(1)Chevalier EAbnormal cytoplasmic localization and accumulation of pathological transactive response DNA binding protein of 43 kDa (TDP-43) underlies several devastating diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). A key element is the correlation between disease progression and spatio-temporal propagation of TDP-43-mediated pathology in the central nervous system. Several lines of evidence support the concept of templated aggregation and cell to cell spreading of pathological TDP-43. To further investigate this mechanism in vivo, we explored the efficacy of capturing and masking the seeding-competent region of extracellular TDP-43 species. For this, we generated a novel monoclonal antibody (mAb), ACI-6677, that targets theActa neuropathologica communications156https://www.ebi.ac.uk/biostudies/studies/S-EPMC11448013biostudies-literatureTargeting the TDP-43 low complexity domain blocks spreading of pathology in a mouse model of ALS/FTD.PMC11448013Chevalier EAfroz TPfeifer APiorkowska KAudrain MRatnam MOllier RSeredenina TKosco-Vilbois MFuchs AfalseTargeting the TDP-43 low complexity domain blocks spreading of pathology in a mouse model of ALS/FTD.Abnormal cytoplasmic localization and accumulation of pathological transactive response DNA binding protein of 43 kDa (TDP-43) underlies several devastating diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). A key element is the correlation between disease progression and spatio-temporal propagation of TDP-43-mediated pathology in the central nervous system. Several lines of evidence support the concept of templated aggregation and cell to cell spreading of pathological TDP-43. To further investigate this mechanism in vivo, we explored the efficacy of capturing and masking the seeding-competent region of extracellular TDP-43 species. For this, we generated a novel monoclonal antibody (mAb), ACI-6677, that targets the2024-01-01T00:00:00Z2024 Oct2025-04-04T02:00:01.11Z2025-04-04T02:00:01.11ZS-EPMC114480133936334810.1186/s40478-024-01867-z