Alzheimer’s disease (AD) is characterized by an amazing interplay between numerous aspects of AD, the membrane lipid composition and metabolism, and, the overproduction of the amyloid-beta peptide (Aβ). This has even led to the hypothesis that the nonpathological role of Aβ and its parent protein might be that of regulators of lipid homeostasis. The most documented lipids involved in AD are sphingolipids and cholesterol. The first AD related suspected lipid from sphingolipid family is the ganglioside GM1 (GM1). A specific Aβ-GM1 complex found in early AD brains, suggested that GM1-bound Aβ may serve as a seed for the formation of toxic amyloid fibrils. Here, we present our results regarding the interaction of Aβ(1–42) with GM1-containing biphasic, liquid ordered/liquid disordered phase (Lo/Ld) giant vesicles. Our fluorescence co-localization experiments confirm that Aβ(1–42) binds preferentially to the Ld phase. The effect of Aβ on the Lo/Ld size dynamics is studied using photoinduced spinodal decomposition which mimics the nanodomain/microdomain raft coalescence. Aβ(1–42) affects the kinetics of the coarsening phase and the size of the resulting microdomains, depending on which phase, Lo, or, Ld, is in a majority. Our fluorimetric measurements on large unilamellar vesicles using the probe Laurdan indicate that Aβ(1–42) binding respectively increases or decreases the packing of the Ld phase in the presence or absence of GM1. The differential effects of Aβ(1–42) on spinodal decomposition are accordingly interpreted as resulting from distinct effects of the peptide on the Lo/Ld line tension modulated by GM1. In all, this study confirms that Aβ(1–42) binds preferentially to the non-raft Ld phase of membranes even in the presence of the ganglioside GM1. Finally, having in mind that the dynamics of raft nano-micro-domains is instrumental in many cell signaling processes, it appears that many neuron signaling processes might be affected at various stages of AD by <u>mechanism related to the <b>kinetics</b> of phase coarsening</u>.

Alzheimer’s disease amyloid-β peptide and the sphingolipids: From lipid domain pattern to functioning

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.