In this study, we directly compared the neurotoxic capacity of CSF obtained from sALS patients and familial amyotrophic lateral sclerosis (fALS) patients with mutations in SOD1, C9orf72 and TARDBP using a novel CSF-mediated mouse model which can reliably detect motor impairments and pathological changes in the spinal cord induced by a single 3 μL injection of CSF into the cervical subarachnoid space. The gene discussed is TARDBP; the disease is familial amyotrophic lateral sclerosis.