Alzheimer's disease (AD) was first described more than 100 years ago and is today the most common cause of dementia. It is one of the progressive neurodegenerative diseases that affect 47 million people around the world between the ages of 60 and 90. One of the contributing factors to AD is extracellular amyloid – β (Aβ) plaques that form as a result of protein aggregation. These Aβ proteins are neurotoxic, leading to degeneration of brain neurons and loss of cognitive abilities. Because AD largely affects society, researchers are constantly working to find a cure, which currently does not exist. The purpose of this study was to use Drosophila melanogaster as a living organism model for the expression of two types of Aβ proteins related to AD, Arctic (Glu22Gly) and TandemAβ, and to study the survival of these AD flies when Bovine serum albumin (BSA) was added to the fly food. The hypothesis was that BSA would be effective in slowing down and/or preventing formation of toxic Aβ-aggregates. The focus was therefore to investigate whether the AD flies would live longer if they were allowed to eat Bovine serum albumin and whether the soluble/insoluble Aβ levels in these flies would decrease in comparison to the control AD flies that were not allowed to eat BSA. The effect of BSA on toxicity was evaluated using survival assay on male flies and the levels of soluble/insoluble Aβ were evaluated using Meso Scale Discovery (MSD) on female flies. In both experiments, the following six groups of flies were examined: myow1118 ± BSA; myoArctic ± BSA; myoTandemAβ ± BSA. Conclusions from the studies are that the survival of AD flies could not be extended by adding 0.61 mM BSA to the food, rather the data showed a weak but significant toxic effect in the presence of BSA in the AD flies. However, MSD data showed a reduction of insoluble Aβ aggregates and an equilibrium shift from insoluble Aβ aggregates to soluble Aβ aggregates in the presence of BSA in the AD flies. Equilibrium shifts were particularly detectable in Myo-TandemAβ flies fed with BSA. In Myo-Arctic flies fed with BSA only reduction of insoluble Aβ could be detected. This shows that it is not the amount of Aβ aggregates that is decisive for toxicity, but rather the presence of specific aggregates that have toxic properties. If BSA shows good results in further studies, it could be used in the future to improve AD symptoms in patients.
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:liu-205082 |
| Date | January 2024 |
| Creators | Tani, Milena |
| Publisher | Linköpings universitet, Institutionen för fysik, kemi och biologi |
| Source Sets | DiVA Archive at Upsalla University |
| Language | Swedish |
| Detected Language | English |
| Type | Student thesis, info:eu-repo/semantics/bachelorThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
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