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The cellular mechanism underlying neuronal changes in Alzheimer's disease


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Dickson, Tracey 2000 , 'The cellular mechanism underlying neuronal changes in Alzheimer's disease', PhD thesis, University of Tasmania.

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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.

Item Type: Thesis - PhD
Authors/Creators:Dickson, Tracey
Keywords: Alzheimer's disease
Copyright Holders: The Author
Copyright Information:

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).

Additional Information:

Thesis (Ph.D.)--University of Tasmania, 2000. Includes bibliographical references

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