Investigating the protective effects of vitamin B12 on amyloid-beta proteotoxicity in a C. elegans model of Alzheimer’s Disease.

• Caden MacHenry, Biological Sciences, University of Delaware

• Jessica Tanis, Biological Sciences, University of Delaware

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects millions of

Americans. Amyloid-beta (Aβ) proteotoxicity contributes to the pathogenesis of AD. Utilizing

the model organism Caenorhabditis elegans, we are identifying factors that impact Aβ

proteotoxicity in vivo. Expression of toxic human Aβ in the C. elegans body wall muscles

causes worms to paralyze and dietary vitamin B12 has a significant effect on time to paralysis.

Since AD is a neurodegenerative disorder, we transitioned focus to C. elegans with neuronal Aβ.

Neuronal Aβ animals have a reduced chemotaxis index (CI) when fed a B12 deficient diet, but a

wild-type CI when given a B12 rich diet. To determine if neuronal Aβ affected learning, worms

were conditioned to isoamyl alcohol in the absence of food before the chemotaxis assay.

Conditioned control worms learned that isoamyl alcohol was associated with starvation, but

neuronal Aβ worms fed a B12-deficient diet exhibited learning defects; dietary supplementation

with B12 restored learning. To determine if these learning deficits are due to defects in the

morphology of the AWC neurons that sense isoamyl alcohol, I crossed worms with the neuronal

Aβ transgene with worms that had a transgene that expresses RFP in the AWB and AWC

neurons. After completing the genetic crosses, I mounted worms on slides with agarose pads and

levamisole to halt movement and imaged them with the Dragonfly Spinning Disk Confocal

Microscope. I predict that worms with neuronal Aβ will have altered AWC neuron morphology

and that growth of these animals with vitamin B12 will lead to healthier neuron morphology due

to the suggested protective effects of vitamin B12. Investigating the relationship between vitamin

B12 and the degradative effects of Aβ allows us to gain a greater understanding of the possible

therapeutic quality of vitamin B12 in slowing the onset of Alzheimer’s disease.