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Neuroimmunol Neuroinflammation 2019;6:15 Neuroimmunology
DOI: 10.20517/2347-8659.2019.019 and Neuroinflammation

Meeting Abstracts Open Access

2019 CNS Diseases: Advanced Diagnostics and
Treatment Conference

Melbourne, Australia; Sep 2019; Published: 30 Dec 2019

Correspondence to: Raghav Gupta, 2019 CNS Diseases committee, Melbourne 3004, Australia.
E-mail: secretary@cnsconference.com

1. Yeast studies on the benefit of simvastatin in reducing levels of amyloid betaian

Macreadie, Sudip Dhakal, Mishal Subhan, Ken Gardiner, Joshua Fraser

RMIT University, Melbourne, Victoria, Australia

A large-scale epidemiology study on statins previously showed that simvastatin was unique among statins
in reducing the incidence of dementia. Since amyloid beta (Aβ42) is the protein that is most associated
with Alzheimer’s disease, this study has focused on how simvastatin influences the turnover of native
Aβ42 and Aβ42 fused with green fluorescent protein (GFP), in the simplest eukaryotic model organism,
saccharomyces cerevisiae. Previous studies have established that yeast constitutively producing Aβ42 fused
to GFP offer a convenient means of analyzing yeast cellular responses to Aβ42. Young cells clear the GFP
fusion protein and do not have green fluorescence while the older population of cells retains the fusion
protein and exhibits green fluorescence, offering a fast and convenient means of studying factors that affect
Aβ42 turnover. In this study the proportion of cells having GFP fused to Aβ after exposure to simvastatin,
atorvastatin and lovastatin was analyzed by flow cytometry. Simvastatin effectively reduced levels of
the cellular Aβ42 protein in a dose-dependent manner. Simvastatin promoted the greatest reduction as
compared to the other two statins. A comparison with fluconazole, which targets that same pathway of
ergosterol synthesis, suggests that effects on ergosterol synthesis do not account for the reduced amounts of
Aβ42 fused to GFP. The levels of native Aβ42 following treated with simvastatin were also examined using
a more laborious approach, quantitative MALDI TOF mass spectrometry. Simvastatin efficiently reduced
levels of native Aβ42 from the population. This work indicates a novel action of simvastatin in reducing
levels of Aβ42 providing new insights into how simvastatin exerts its neuroprotective role. This reduction is
likely to be due to protein clearance.

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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