ALS is a progressive neurodegenerative disorder characterized by motor neuron death. Only 5-10% of ALS cases are familial (fALS) while the majority occur sporadically (sALS). One hallmark of ALS is TDP-43 aggregation in the cytoplasm. We previously reported that intrathecal delivery of sALS, but not fALS CSF, induces motor deficits and motor neuron degeneration in mice. Here, we investigated whether differences in CSF neurotoxicity are associated with induction of pathological TDP-43 expression.

CSF obtained from sALS and fALS patients was delivered intrathecally to 8-10-week-old female C57BL/6 mice. Mice were injected with 3uL of sALS, SOD1, C9orf72, TARDBP CSF or 5kDa filtered sALS CSF. 5kDa filtered sALS CSF was obtained by passing sALS CSF through a 5kDa hollow-fiber filter. Control mice received either saline, CSF from healthy individuals or multiple sclerosis patients. Forelimb deficits were assessed at 1-day post injection (DPI), then mice were perfused for histological analysis. TDP-43 localization was assessed by co-staining tissue with anti-TDP-43 and anti-ChAT antibodies.