Year

2019

Degree Name

Doctor of Philosophy

Department

School of Biological Sciences

Abstract

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterised by cognitive deficit and memory loss. The pathological hallmarks of the disease are the deposition of extracellular amyloid plaques containing high levels of amyloid β 42/40 and intracellular neurofibrillary tangles containing hyperphosphorylated tau together with brain atrophy. AD can be divided into two types: Familial AD, also known as early-onset AD, accounts for less than 5% of all AD cases and it is caused by known mutations in APP, PSEN1 and PSEN2 genes, involved in the processing of the amyloid precursor protein. Sporadic AD, also known as late-onset AD, is the most common form of AD and likely caused by genetic variations in many genes. The presence of the ɛ4 allele of the APOE gene is the major genetic risk factor of AD. The APOE gene codes for apolipoprotein E (apoE), a 35-kDa glycoprotein highly expressed in the brain with a major role in lipid transport. There are three different isoforms of apoE in humans: apoE3 is the most common isoform in the population, apoE2 reduces the risk of AD and apoE4 increases the risk of AD. These isoforms differ in just two amino acids, which alters protein stability and leads to differences in the fragmentation of apoE.

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Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.