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• W2894965458 abstract "The stereotypical distribution of TAR DNA-binding 43 protein (TDP-43) aggregates in frontotemporal lobar degeneration (FTLD-TDP) suggests that pathological TDP-43 spreads throughout the brain via cell-to-cell transmission and correlates with disease progression, but no in vivo experimental data support this hypothesis. We first develop a doxycycline-inducible cell line expressing GFP-tagged cytoplasmic TDP-43 protein (iGFP-NLSm) as a cell-based system to screen and identify seeding activity of human brain-derived pathological TDP-43 isolated from sporadic FTLD-TDP and familial cases with Granulin (FTLD-TDP-GRN) or C9orf72 repeat expansion mutations (FTLD-TDP-C9+). We demonstrate that intracerebral injections of biologically active pathogenic FTLD-TDP seeds into transgenic mice expressing cytoplasmic human TDP-43 (lines CamKIIa-hTDP-43NLSm, rNLS8, and CamKIIa-208) and non-transgenic mice led to the induction of de-novo TDP-43 pathology. Moreover, TDP-43 pathology progressively spreads throughout the brain in a time-dependent manner via the neuroanatomic connectome. Our study suggests that the progression of FTLD-TDP reflects the templated cell-to-cell transneuronal spread of pathological TDP-43." @default.
• W2894965458 created "2018-10-12" @default.
• W2894965458 creator A5006999330 @default.
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• W2894965458 date "2018-10-11" @default.
• W2894965458 modified "2023-10-14" @default.
• W2894965458 title "Patient-derived frontotemporal lobar degeneration brain extracts induce formation and spreading of TDP-43 pathology in vivo" @default.
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• W2894965458 doi "https://doi.org/10.1038/s41467-018-06548-9" @default.
• W2894965458 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6181940" @default.
• W2894965458 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30310141" @default.
• W2894965458 hasPublicationYear "2018" @default.
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