Glutamatergic neuron degeneration in C. elegans models of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

Abstract

Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) overlap considerably in genetic origin and pathology. Multiple C. elegans models of ALS/FTD have been developed, but the integrity of glutamatergic neurons in these models has not been thoroughly evaluated. Here, we report degeneration of glutamatergic phasmid neurons in animals expressing either wild-type or disease variant V337M human tau, and mild degeneration in animals expressing disease variant M337V human TDP-43. Defects caused by ectopic expression of tau were suppressed by loss of the known modifier, spop-1 , suggesting that SPOP-1-dependent pathways are also involved in glutamatergic neuron degeneration.