Effects of system complexity on protein aggregation in neurodegeneration
type: CreativeWork
description: Alzheimer's disease (AD) is a neurodegenerative disorder, the leading cause of dementia worldwide, and is one of the most pressing challenges in ageing societies. The disease is characterised by extensive brain atrophy, synaptic loss, and the accumulation of two types of protein aggregates: amyloid β (Aβ) plaques and tau neurofibrillary tangles. The deposition of Aβ can be causally linked to familial and early onset AD, however Aβ-targeting treatments against the more common sporadic form of the disease have so far shown limited to no efficacy. If early onset AD can be considered an autosomal dominant disease, sporadic AD is multi-factorial, and it might not have a unique cause. Indeed, the two largest risk factors for late-onset AD are not linked directly with Aβ processing: the first one being age and the second being the isoform APOE4 of the lipoprotein APOE—which is involved in lipid and cholesterol metabolism. In light of the high-dimensionality of this problem, in my thesis I will follow a bottom-up (biophysics to systems biology) approach in dealing with the influence of systemic complexity in protein aggregation across different components of cellular homoeostasis, in particular lipid membranes and the proteostasis network. In the first chapter of the thesis, I will present a selection of the scientific literature on AD, with a particular focus on systemic aspects, such as cellular networks of quality control, protein co-aggregation, and ageing. The second chapter will address the relationship between protein aggregation and the complexity of the lipid environment in which it occurs. This will be done by studying the aggregation of recombinant Aβ (rAβ) peptide in vitro in presence of model lipid membranes. After describing the theoretical foundations of the study of protein aggregation via means of chemical kinetics, I will show how different lipid species affect the aggregation kinetics of rAβ42 and highlight on how lipid-peptide interactions affect the abi…
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder, the leading cause of dementia worldwide, and is one of the most pressing challenges in ageing societies. The disease is characterised by extensive brain atrophy, synaptic loss, and the accumulation of two types of protein aggregates: amyloid β (Aβ) plaques and tau neurofibrillary tangles. The deposition of Aβ can be causally linked to familial and early onset AD, however Aβ-targeting treatments against the more common sporadic form of the disease have so far shown limited to no efficacy. If early onset AD can be considered an autosomal dominant disease, sporadic AD is multi-factorial, and it might not have a unique cause. Indeed, the two largest risk factors for late-onset AD are not linked directly with Aβ processing: the first one being age and the second being the isoform APOE4 of the lipoprotein APOE—which is involved in lipid and cholesterol metabolism. In light of the high-dimensionality of this problem, in my thesis I will follow a bottom-up (biophysics to systems biology) approach in dealing with the influence of systemic complexity in protein aggregation across different components of cellular homoeostasis, in particular lipid membranes and the proteostasis network. In the first chapter of the thesis, I will present a selection of the scientific literature on AD, with a particular focus on systemic aspects, such as cellular networks of quality control, protein co-aggregation, and ageing. The second chapter will address the relationship between protein aggregation and the complexity of the lipid environment in which it occurs. This will be done by studying the aggregation of recombinant Aβ (rAβ) peptide in vitro in presence of model lipid membranes. After describing the theoretical foundations of the study of protein aggregation via means of chemical kinetics, I will show how different lipid species affect the aggregation kinetics of rAβ42 and highlight on how lipid-peptide interactions affect the abi…
author: Sanguanini, Michele
language: eng
keywords: ageing, protein aggregation, alzheimer's disease, multiomics
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/8dce8f2b-858b-46e4-b8ce-8a180d60c343/download
license: https://creativecommons.org/licenses/by-nc/4.0/
date published: 2021-10-30
date modified: 2026-07-22T22:24:25Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.71909