APP and amyotrophic lateral sclerosis: Furthermore, the formation of perikaryal/axonal intermediate filament inclusions, neurofilament abnormalities and genetic defects in microtubule-based transport that may facilitate the elevation of the toxic amyloid beta precursor in ALS (Spadoni et al., 2009; Bryson et al., 2012) might correlate the downregulation of App seen in the spinal cord of 80 days presymptomatic phase to a neuroprotective regulation before the neuronal death onset.