For the first time, we assessed neurodegeneration in relation to α-synuclein pathology by quantitating the number of motor neurons and pS129 α-synuclein immunoreactivity in spinal cord following intraperitoneal injection of assembled recombinant human A53T α-synuclein or cerebellar extract from a case with type II MSA filaments, as determined by electron cryo-microscopy (cryo-EM), thereby establishing a direct correlation between a specific MSA filament type and neurodegeneration. This evidence concerns the gene SNCA and multiple system atrophy.