{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Zhong W"],"funding":["Swiss National Science Foundation","NINDS NIH HHS"],"pubmed_abstract":["Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) shows striking clinical and neuropathological heterogeneity, yet a systematic analysis of subtype-specific features and inter-patient variability was missing. We treated human neurons and neuron-like cells with 30 postmortem brain samples and quantified neoaggregate formation, loss of function and changes in the TDP-43 interactome to define determinants of seeding outcomes. Potent FTLD-TDP-A seeds drove a progressive collapse of physiological TDP-43 interactions accompanied by functional loss. Beyond the burden of pathological TDP-43, we identified the fibrillar core of the lysosomal protein TMEM106B as a critical pro-seeding factor. Transient lysosomal injury markedly enhanced neoaggregation and loss of function, likely b"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.12.19.695531"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12767511"],"repository":["biostudies-literature"],"pubmed_title":["Lysosomal escape and TMEM106B fibrillar core determine TDP-43 seeding outcomes."],"pmcid":["PMC12767511"],"funding_grant_id":["320030","RM1 NS133601"],"pubmed_authors":["Lim SM","Hafliger M","de Cecco E","Peter M","Manglunia R","Lagier-Tourenne C","Ramesh N","Ward M","Zhong W","Wilkins OG","Fratta P","Polymenidou M","Scialo C","Jagannath S","Gatta B","Leu N","Lurati F","Roschitzki B","Aguzzi A","Petrucelli L"],"additional_accession":[]},"is_claimable":false,"name":"Lysosomal escape and TMEM106B fibrillar core determine TDP-43 seeding outcomes.","description":"Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) shows striking clinical and neuropathological heterogeneity, yet a systematic analysis of subtype-specific features and inter-patient variability was missing. We treated human neurons and neuron-like cells with 30 postmortem brain samples and quantified neoaggregate formation, loss of function and changes in the TDP-43 interactome to define determinants of seeding outcomes. Potent FTLD-TDP-A seeds drove a progressive collapse of physiological TDP-43 interactions accompanied by functional loss. Beyond the burden of pathological TDP-43, we identified the fibrillar core of the lysosomal protein TMEM106B as a critical pro-seeding factor. Transient lysosomal injury markedly enhanced neoaggregation and loss of function, likely b","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-04T03:21:44.073Z","creation":"2026-06-04T03:12:35.103Z"},"accession":"S-EPMC12767511","cross_references":{"pubmed":["41497595"],"doi":["10.64898/2025.12.19.695531"]}}