PROTON magnetic resonance spectroscopy (1H-MRS) was used to measure thein vivosignal ofN-acetylaspartate (NAA), a putative neuronal marker, in the brain of the mutant wobbler mouse, a model of motor neuron disease. The ratio of NAA to creatine-phosphocreatine, an internal standard, was significantly lower in five affected wobbler mice (0.79 ± 0.05; mean ± s.d.) than in five unaffected littermates (0.98 ± 0.10,p= 0.006). Ubiquitin and phosphorylated heavy neurofilament immunoreactivities were increased in cortical neurons of affected animals. This is the first demonstration of cerebral neuronal pathology in the wobbler mouse, supporting its use as a model of amyotrophic lateral sclerosis.In vivo1H-MRS and correlative postmortem study of wobbler mouse brain will allow temporal monitoring of neuronal degeneration and responsiveness to neuro-protective pharmacotherapies.