Investigating the Role of Plasmalogens in C. elegans

Hickman, Anna; Murray, Sofi

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Investigating the Role of Plasmalogens in C. elegans

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Plasmalogens, a class of ether-linked phospholipids found in cell membranes, are decreased in patients with Alzheimer’s disease. Therefore, plasmalogens have potential to be targeted as a biomarker or even as a therapeutic for the treatment of the disease. Recently, a clinical trial showed improvement in cognitive function in specific populations with mild cognitive impairment (MCI) suggesting that plasmalogen supplementation therapy may be a viable option for ameliorating MCI and Alzheimer’s disease. However, the mechanism of plasmalogen function in MCI and Alzheimer’s disease has not been elucidated. Here, we use a recently developed model of plasmalogen deficiency in C. elegans to probe the impact of plasmalogen supplementation. Specifically, we reduced the amount of plasmalogen biosynthesis genes, FARD-1 and ADS-1, by RNAi, and then investigated the impact of plasmalogen supplementation on the lipid profile of these models. We coupled the lipidomic analysis by HPLC-MS/MS with small scale experiments to attempt to rescue the phenotypes of the plasmalogen deficient models including brood size, reaction to heat and oxidative stress. Our analysis did not show significant incorporation into the lipids of the wild-type or rescue of the phenotypes of the plasmalogen deficiency models. Because lipase activity is required for lipid absorption in the intestine, the lack of rescue suggests that the plasmalogen supplement is not increasing the levels of plasmalogens and may not be a viable option for therapy.

This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

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