Abstract

Neurodegenerative diseases predominantly affect older cohorts, but the disease progression occurs from earlier in adult life. The ability to monitor early mobility decline throughout adulthood, i.e. prior to the onset of severe symptoms in old age, can inform the search for preventative interventions and the understanding of disease onset mechanisms.

There are several C. elegans models of neurodegeneration but manual assays are subjective, labour intensive and provide binary data at single time points per animal – namely time of paralysis. Magnitude Biosciences’ automated imaging system monitors worm movement while simultaneously revealing in-depth movement data unavailable to manual methods and is scalable to study hundreds of plates of animals. Additionally, manual assays disproprotionately use muscle-expressing strains, due to their clear phenotypic effects on mobility, but neuron-expressing strains are more physiologically relevant.

Magnitude Biosciences technology near-continuously monitors up to 90 6 cm petri dishes, with 30 worms per dish, up to 10 days. Using strains expressing polyglutamine (Huntington’s disease) and amyloid-beta (Alzheimer disease), we show that these transgenes are associated with movement decline trackable throughout the life course, in both muscle and neuron-expressing strains.

Separately, tracking mobility throughout adulthood allows to detect time-dependent effects of age-related diseases interventions. By exposing a wild-type C. elegans strain to metformin, rapamycin, alpha-ketoglutarate and resveratrol, we detected a diversity of mobility effects at either middle or late adulthood, which is informative not only of mode of action but can inform age-specific timing for administration to patients.