A hypothesis for the pathogenesis of amyotrophic lateral sclerosis.

The microscopic pathology of spinal cord and brain in ALS has suggested that the earliest abnormality is a progressive depletion of dendritic neurofilaments leading to dendritic atrophy, vulnerability to breakage and attrition. We hypothesize that this in turn will lead to shrinkage and eventual death of the perikaryon. This hypothesis could explain the preferential vulnerability of the spinal, corticospinal and cortico-bulbar neurons to damage and death in ALS because only these neurons contain conspicuous bundles of neurofilaments in dendrites. Agents or factors that could subvert the transport or the integrity of dendritic neurofilaments should be sought in ALS.