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Defining the earliest pathological changes of Alzheimer's disease
Citation
Vickers, J and Mitew, S and Woodhouse, A and Fernandez-Martos, CM and Kirkcaldie, MT and Canty, AJ and McCormack, GH and King, AE, Defining the earliest pathological changes of Alzheimer's disease, Current Alzheimer research, 13, (3) pp. 281-287. ISSN 1567-2050 (2016) [Refereed Article]
Copyright Statement
Copyright 2016 Bentham Science Publishers
DOI: doi:10.2174/1567205013666151218150322
Abstract
The prospects for effectively treating well-established dementia, such as Alzheimer's disease (AD), are slim, due to the destruction of key brain pathways that underlie higher cognitive function. There has been a substantial shift in the field towards detecting conditions such as AD in their earliest stages, which would allow preventative or therapeutic approaches to substantially reduce risk and/or slow the progression of disease. AD is characterized by hallmark pathological changes such as extracellular Aß plaques and intracellular neurofibrillary pathology, which selectively affect specific subclasses of neurons and brain circuits. Current evidence indicates that Aß plaques begin to form many years before overt dementia, a gradual and progressive pathologywhich offers a potential target for early intervention. Early Aß changes in the brain result in localized damage to dendrites, axonal processes and synapses, to which excitatory synapses and the processes of projection neurons are highly vulnerable. Aß pathology is replicated in a range of transgenic models overexpressing mutant human familial AD genes (eg APP and presenilin 1). Studying the development of aberrant regenerative and degenerative changes in neuritic processes associated with Aß plaques may represent the best opportunity to understand the relationship between the pathological hallmarks of AD and neuronal damage, and to develop early interventions to prevent, slow down or mitigate against Aß pathology and/or the neuronal alterations that leads to cognitive impairment.
Item Details
Item Type: | Refereed Article |
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Keywords: | Alzheimer's disease, preclinical, synapses, amyloid precursor protein, Aß, plaque, dystrophic neurite, selective vulnerability, transgenic mice |
Research Division: | Biomedical and Clinical Sciences |
Research Group: | Neurosciences |
Research Field: | Cellular nervous system |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Vickers, J (Professor James Vickers) |
UTAS Author: | Mitew, S (Mr Stanislaw Mitew) |
UTAS Author: | Woodhouse, A (Dr Adele Woodhouse) |
UTAS Author: | Fernandez-Martos, CM (Dr Carmen Fernandez-Martos) |
UTAS Author: | Kirkcaldie, MT (Dr Matthew Kirkcaldie) |
UTAS Author: | Canty, AJ (Associate Professor Alison Canty) |
UTAS Author: | McCormack, GH (Mr Graeme McCormack) |
UTAS Author: | King, AE (Professor Anna King) |
ID Code: | 105731 |
Year Published: | 2016 |
Web of Science® Times Cited: | 31 |
Deposited By: | Medicine |
Deposited On: | 2016-01-13 |
Last Modified: | 2018-03-20 |
Downloads: | 0 |
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