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The role of TDP-43 in Alzheimer’s disease

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posted on 2024-07-19, 04:51 authored by Takudzwa Chivazve

Dementia is described clinically as a progressive deterioration of cognitive function that intervenes with daily life. Alzheimer’s disease (AD) is the most common of the dementias. In 2019, dementia was classified as the 7th leading cause of death globally among all ages. The distinguishing feature of AD is the progressive neurodegeneration caused by abnormal expressions of amyloid beta (Aβ) plaques and neurofibrillary tangles. Recent literature has introduced the idea that TDP-43 facilitates a role in AD pathology. The nature of TDP-43-mediated neuronal loss remains heavily debated. During neurodegeneration, TDP-43 is expelled from the nucleus and aggregates in the cytoplasm. The neuronal loss is said to be either mediated by the loss of normal function in the nucleus or a toxic gain of function caused by the aggregation in the cytoplasm. The aim of the project was to investigate the effect of knocking down TDP-43 protein in APP23 mice models. It was hypothesised a knockdown to TDP-43 in APP23 mice models would result in a TDP-43 loss of function leading to an exacerbation in AD-like symptoms. In this study, we showed the TDP-43 knockdown exacerbated motor deficits and AD-like cognitive decline when compared to APP23 mice expressing GFP. The research project led to the acquisition of enhanced knowledge while providing a foundation for future experiments to study the interactions of TDP-43 in the context of AD in greater detail. This knowledge will remain critical in clinical implications and unlocking potential therapeutics involving TDP-43 for enhanced patient outcomes.

History

Table of Contents

Chapter 1: Introduction -- Chapter 2: Method -- Chapter 3: Results -- Chapter 4: Discussion -- References

Awarding Institution

Macquarie University

Degree Type

Thesis MRes

Degree

Master of Research

Department, Centre or School

Macquarie Medical School

Year of Award

2024

Principal Supervisor

Annika van Hummel

Additional Supervisor 1

Yazi Ke

Rights

Copyright: The Author Copyright disclaimer: https://www.mq.edu.au/copyright-disclaimer

Language

English

Extent

61 pages

Former Identifiers

AMIS ID: 338834

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