Differential vulnerability among motor neuron (MN) subtypes is a fundamental feature of amyotrophic lateral sclerosis (ALS):Amyotrophic lateral sclerosis (ALS) is an adult-onset, fatal neurodegenerative disease characterized by progressive degeneration of motor neurons (MNs) and skeletal muscle denervation and atrophy. However, strong evidence suggests the MN pools involved in eye movement and pelvic sphincter control are largely spared in ALS 1,2 . Moreover, within a given MN pool, differences in vulnerability between MN subtypes (e.g. alpha/gamma or fast/ slow) are a fundamental but unexplained feature of ALS. α -MNs are divided into three subtypes: fast-twitch fatigable (FF), fast-twitch fatigue-resistant (FR) and slow-twitch fatigue-resistant (S). The large-diameter low-excitability FF MNs innervate type IIB muscle fibers and degenerate early in the ALS disease course, while medium-excitability FR MNs innervating type IIA muscle fibers follow after that. The high-excitability S MNs innervating type I muscle fibers are largely resistant to degeneration and are preserved, even late in the disease course. Although molecular markers for MNs have been available for several years [3][4][5][6] , the absence of markers that distinguish FF from FR MNs has hindered analysis of the early selective degeneration of MN subtypes.

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