A novel approach to study the effects of the high-fat diet on markers of Alzheimer’s disease in a genetically stratified Drosophila population

A high-fat diet is emerging as a particularly influential risk factor for Alzheimer’s disease due to the strong association with gut dysbiosis, inflammation, oxidative and metabolic stress, and cognitive deficits. We suggest that disturbed cholesterol biosynthesis and metabolism are one of the major...

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Main Author: Yarosh, Vladyslava
Format: Thesis (University of Nottingham only)
Language:English
Published: 2023
Subjects:
Online Access:https://eprints.nottingham.ac.uk/74539/
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author Yarosh, Vladyslava
author_facet Yarosh, Vladyslava
author_sort Yarosh, Vladyslava
building Nottingham Research Data Repository
collection Online Access
description A high-fat diet is emerging as a particularly influential risk factor for Alzheimer’s disease due to the strong association with gut dysbiosis, inflammation, oxidative and metabolic stress, and cognitive deficits. We suggest that disturbed cholesterol biosynthesis and metabolism are one of the major factors through which the diet can exert its influence on the markers of neurodegeneration. The blood-brain barrier (BBB) is an important protective mechanism which helps maintain cholesterol homeostasis and diet-induced oxidative stress is associated with its damage. We investigated the effects of the high-fat diet on these processes by assessing the brain cholesterol pool, lipid peroxidation levels, and morphological neurodegeneration of Drosophila mutants with familial and sporadic genetic predisposition. We also adapted two additional protocols which will be useful in further investigation of the role of high-fat in Alzheimer’s pathology: 1) assessment of the BBB integrity and 2) testing of the short- and long-term memory deficits using a T-Maze manufactured using a 3D Printer. Our findings demonstrate that the high-fat diet disturbs cholesterol homeostasis in both mutant groups, but lipid peroxidation and neurodegeneration are characteristic of familial mutants that present with much earlier disease onset.
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spelling nottingham-745392025-06-03T12:38:03Z https://eprints.nottingham.ac.uk/74539/ A novel approach to study the effects of the high-fat diet on markers of Alzheimer’s disease in a genetically stratified Drosophila population Yarosh, Vladyslava A high-fat diet is emerging as a particularly influential risk factor for Alzheimer’s disease due to the strong association with gut dysbiosis, inflammation, oxidative and metabolic stress, and cognitive deficits. We suggest that disturbed cholesterol biosynthesis and metabolism are one of the major factors through which the diet can exert its influence on the markers of neurodegeneration. The blood-brain barrier (BBB) is an important protective mechanism which helps maintain cholesterol homeostasis and diet-induced oxidative stress is associated with its damage. We investigated the effects of the high-fat diet on these processes by assessing the brain cholesterol pool, lipid peroxidation levels, and morphological neurodegeneration of Drosophila mutants with familial and sporadic genetic predisposition. We also adapted two additional protocols which will be useful in further investigation of the role of high-fat in Alzheimer’s pathology: 1) assessment of the BBB integrity and 2) testing of the short- and long-term memory deficits using a T-Maze manufactured using a 3D Printer. Our findings demonstrate that the high-fat diet disturbs cholesterol homeostasis in both mutant groups, but lipid peroxidation and neurodegeneration are characteristic of familial mutants that present with much earlier disease onset. 2023-12-13 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/74539/1/25-08-2023%20-%20YAROSH%2C%20Vladyslava%2020410352.pdf Yarosh, Vladyslava (2023) A novel approach to study the effects of the high-fat diet on markers of Alzheimer’s disease in a genetically stratified Drosophila population. MRes thesis, University of Nottingham. Alzheimer’s disease; Risk factors; Cholesterol biosynthesis; Neurodegeneration; Blood-brain barrier; Cholesterol homeostasis; Diet-induced oxidative stress
spellingShingle Alzheimer’s disease; Risk factors; Cholesterol biosynthesis; Neurodegeneration; Blood-brain barrier; Cholesterol homeostasis; Diet-induced oxidative stress
Yarosh, Vladyslava
A novel approach to study the effects of the high-fat diet on markers of Alzheimer’s disease in a genetically stratified Drosophila population
title A novel approach to study the effects of the high-fat diet on markers of Alzheimer’s disease in a genetically stratified Drosophila population
title_full A novel approach to study the effects of the high-fat diet on markers of Alzheimer’s disease in a genetically stratified Drosophila population
title_fullStr A novel approach to study the effects of the high-fat diet on markers of Alzheimer’s disease in a genetically stratified Drosophila population
title_full_unstemmed A novel approach to study the effects of the high-fat diet on markers of Alzheimer’s disease in a genetically stratified Drosophila population
title_short A novel approach to study the effects of the high-fat diet on markers of Alzheimer’s disease in a genetically stratified Drosophila population
title_sort novel approach to study the effects of the high-fat diet on markers of alzheimer’s disease in a genetically stratified drosophila population
topic Alzheimer’s disease; Risk factors; Cholesterol biosynthesis; Neurodegeneration; Blood-brain barrier; Cholesterol homeostasis; Diet-induced oxidative stress
url https://eprints.nottingham.ac.uk/74539/