University of Tasmania
whole_DicksonTracey2000_thesis.pdf (17.74 MB)

The cellular mechanism underlying neuronal changes in Alzheimer's disease

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posted on 2023-05-26, 23:27 authored by Dickson, Tracey
The cause of the degeneration of nerve cells, and the loss of specific synaptic connections, that underlies the emergence and progressive development of dementia in sufferers of Alzheimer's disease remains elusive. Furthermore, although individually the B-amyloid plaque, neurofibrillary tangle and dystrophic neurite, pathological hallmarks of the disease, have been extensively investigated, the mechanism that links these structures also remains to be defined. This thesis, therefore, sought to address three aims that were principally associated with the relationship between the pathological structures and the mechanism underlying Alzheimer's disease. Firstly, to determine the neurochemical and morphological diversity of abnormal neurites associated with B-amyloid plaque formation in the early and late stages of Alzheimer's disease. Secondly, to examine the relationship between apolipoprotein E immunolabelling and 13-amyloid deposition, neuritic plaques and neurofibrillary tangles using immunofluorescent double labeling techniques. Finally, to develop an in vitro experimental model that mimics the effects of B-amyloid plaques on surrounding neuronal processes. The major conclusions from these investigations were that the dystrophic neurites associated with subsets of B-amyloid plaques develop through a distinct morphological and neurochemical sequence. This sequence of change is intimately linked to various components of the neuronal cytoskeleton, including neurofilaments. The similarity between these changes and those present within axons undergoing a response to physical damage lead to the development of a new hypothesis that B-amyloid plaque deposition causes physical damage to surrounding neurites which results in the formation of dystrophic neurites. This hypothesis was further supported by results obtained from an in vitro model of physical damage. In summary, this study further clarified the relationship between 13- amyloid plaques and dystrophic neurites, particularly with regard to determining the role of specific cytoskeletal changes. Identification of the earliest pathological changes that occur in Alzheimer's disease is necessary for the development of effective therapeutic strategies aimed at preventing or slowing the ongoing neuronal changes that ultimately lead to cell death and dementia.


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Copyright 2000 the Author - The University is continuing to endeavour to trace the copyright owner(s) and in the meantime this item has been reproduced here in good faith. We would be pleased to hear from the copyright owner(s). Thesis (Ph.D.)--University of Tasmania, 2000. Includes bibliographical references

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