An investigation of biological markers in familial and sporadic forms of Alzheimer's disease

Anastazija Gnjec

    Research output: ThesisDoctoral Thesis

    71 Downloads (Pure)


    [Truncated] Alzheimer's disease (AD), the most common form of dementia world-wide, is characterized by progressive cognitive impairment leading to absolute dependence on external care in the later stages of the disease. To date there is no cure for this devastating disorder and definitive diagnosis can only be established after death through postmortem examination of the brain tissue. The neuropathological hallmarks of AD include neurofibrillary tangles and extracellular deposits of β-amyloid peptide (Aβ) in senile plaques and around blood vessels in the brain. These microscopic lesions have been extensively study in the quest to unravel the mysteries of AD pathology. However, numerous intricacies of the underlying pathogenic mechanisms remain elusive. In order to gain a more thorough understanding of the pathogenic processes it is imperative to extend the horizons of research to examination of novel biomarkers that may hold the key to enable earlier diagnosis and may provide effective and safe targets for therapeutic intervention.

    The current study represents an investigation of known biomarkers as well as a search for novel biomarkers of relevance to AD pathology. Protein markers were explored in human AD brain tissue in both familial and sporadic forms of AD. In addition, genetically modified mouse models of AD were employed since this allowed for controlled manipulation of and observation of effects of hormones on AD pathology. A range of techniques was used, including two-dimensional electrophoresis for comparison of protein profiles between AD and control cases. Data presented in this thesis implicates four separate mechanisms in AD pathology. These are inflammation, oxidative stress, impairment of long-term neuronal potentiation and neuronal cell-cycle re-entry.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • The University of Western Australia
    Publication statusUnpublished - 2005

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