Bacterial Lipids Induced Amyloid Assembly and Disease Etiology Open Access

Cen, Siying (Fall 2018)

Permanent URL:


Amyloid has been connected with protein misfolding diseases from the beginning, yet no clear mechanism for neurodegenerative diseases is currently proposed. One proposal is that the gut microbiome plays a role in the formation of amyloid plaques in the human brain. To evaluate the hypothesis that lipopolysaccharides (LPS) from gram-negative bacteria’s membrane participates in the Alzheimer’s disease (AD) at the molecular level, I have tested a model for β-amyloid (Aβ) peptides associating with LPS from gram-negative bacteria membrane, specifically determining whether the lipid A from LPS co-assembles with Aβ (16-22), the nucleating core of Aβ, and its congeners. In the experiments, lipid A and Aβ (16-22) were co-assembled in both aqueous and organic solutions, and the resulting structures characterized with TEM and ATR-FTIR. A type of glycerophospholipid, phosphatidylinositol (PI), was employed as a more soluble and simplified lipid A to mimic the co-assembling of lipid A and Aβ (16-22). My experiments demonstrate a direct interaction between LPS and Aβ (16-22) and CD results support the ability of LPS to induce β-sheet formation in soluble amyloid peptides. In summary, my research supports a direct association between Aβ peptides and LPS, the main component of bacterial outer membrane, but further experiments are needed to reveal the mechanism of LPS-Aβ peptides interaction, which may help explain the etiology of Alzheimer’s disease and bacterial toxicity.

Table of Contents

Abstract 4


List of Figures. 11

List of Tables. 13

Chapter 1. Background. 1

Bacteria and neurodegenerative diseases. 1

Alzheimer’s disease and the amyloid peptide self-assembly. 1

Lipid-amyloid interactions and antimicrobial property of amyloid. 2

Potential of constructing co-assemblies of amyloid with lipids. 4

References. 6

Chapter 2. Exploring the interaction between LPS and amyloid peptide. 10

Introduction. 10

Methods. 11

Peptide synthesis and purification. 11

Peptide Assembly. 12

LPS assembly and LPS-Aβ incubation. 12

Transmission Electron Microscopy (TEM) 13

Circular Dichroism spectroscopy: 13

Results. 14

Characterizing the interaction between Aβ(16-22) peptide and LPS. 14

Time-dependent interaction of Aβ(1-40) and LPS. 18

Conclusion. 19

References. 19

Chapter 3. Defining the structure of lipid A-amyloid assembly 20

Introduction. 20

Methods. 21

Lipid A assembly. 21

Results. 22

TEM images of Aβ(16-22)-lipid A co-assemblies 22

pH-dependent co-assembly process 25

ATR-FTIR measurement of lipid A-Aβ (16-22) co-assemblies 27

Conclusion. 28

References. 33

Chapter 4. Constructing other lipid-amyloid assembly. 34

Introduction. 34

Experiment 35

PI Incubation. 35

Results. 36

Aβ(16-22) and PI assembly process 36

Conclusion. 39

Reference. 39

Chapter 5. Conclusion and perspectives 40

Conclusion. 43

Perspectives. 28

Define the structure of lipid A/Aβ (16-22) assemblies 28

About this Master's Thesis

Rights statement
  • Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.
  • English
Research Field
Committee Chair / Thesis Advisor
Last modified

Primary PDF

Supplemental Files