College Honors Program

High Glucose Has Sex-Specific Effects on Amyloid-β Accumulation in Alzheimer's C. elegans Model

Date of Creation

5-1-2022

Document Type

Campus Access Only

First Advisor

Michelle Mondoux

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that has no known cure or treatment. The Alzheimer's Association predicts 12.7 million people, age 65 and older, will have AD by 2050. There also appears to be sex-specific differences influencing AD progression because almost 2/3 of Americans with AD are women. Furthermore, amyloid β plaques (Aβ) are associated with the neurodegenerative pathology of AD. In humans, glucose is a key component of the diet but has also been shown to have negative health effects, including obesity, diabetes, and a range of illnesses. The effect of a high sugar diet on the development of AD is unknown. The nematode C. elegans has been a successful model of both neurodegenerative diseases like AD and the effects of a high-glucose diet. Transgenic animals expressing human Aβ form plaques, which in turn paralyze the worms. Previous studies in C. elegans have shown that glucose reduces the formation of amyloid β plaques in hermaphrodites, however the effect on males is unknown, and these mechanisms that connect glucose and Aβ accumulation are not fully understood. I found that high glucose diet delays paralysis in hermaphrodite worms, while increasing paralysis in male worms, indicating that glucose has sex-specific effects on Aβ plaque accumulation. Understanding the effects of diet and sex on Aβ formation is essential in informing rational design of AD interventions.

Comments

Reader: Ann Sheehy

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