TDP-43 forms cytoplasmic aggregates in degenerating neurons of frontotemporal dementia (FTD) patients. Laferrière et al. now establish that TDP-43 assemblies from distinct FTD subtypes have different structures, neurotoxicities, and seeding activities, which correlate with FTD severity. Thus, distinct pathological TDP-43 assemblies akin to prion strains might underpin distinct FTD subtypes.
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The authors declare no competing interests.
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Barbieri, E.M., Shorter, J. TDP-43 shapeshifts to encipher FTD severity. Nat Neurosci 22, 3–5 (2019). https://doi.org/10.1038/s41593-018-0299-6
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