Accumulating evidence from mice expressing ALS-causing mutations in superoxide 
dismutase (SOD1) has implicated pathological immune responses in motor neuron 
degeneration. This includes microglial activation, lymphocyte infiltration, and 
the induction of C1q, the initiating component of the classic complement system 
that is the protein-based arm of the innate immune response, in motor neurons of 
multiple ALS mouse models expressing dismutase active or inactive SOD1 mutants. 
Robust induction early in disease course is now identified for multiple 
complement components (including C1q, C4, and C3) in spinal cords of SOD1 
mutant-expressing mice, consistent with initial intraneuronal C1q induction, 
followed by global activation of the complement pathway. We now test if this 
activation is a mechanistic contributor to disease. Deletion of the C1q gene in 
mice expressing an ALS-causing mutant in SOD1 to eliminate C1q induction, and 
complement cascade activation that follows from it, is demonstrated to produce 
changes in microglial morphology accompanied by enhanced loss, not retention, of 
synaptic densities during disease. C1q-dependent synaptic loss is shown to be 
especially prominent for cholinergic C-bouton nerve terminal input onto motor 
neurons in affected C1q-deleted SOD1 mutant mice. Nevertheless, overall onset 
and progression of disease are unaffected in C1q- and C3-deleted ALS mice, thus 
establishing that C1q induction and classic or alternative complement pathway 
activation do not contribute significantly to SOD1 mutant-mediated ALS 
pathogenesis in mice.