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Does Beta-Amyloid Plaque Formation Cause Structural Injury to Neuronal Processes?


Woodhouse, A and West, AK and Chuckowree, JA and Vickers, JC and Dickson, TC, Does Beta-Amyloid Plaque Formation Cause Structural Injury to Neuronal Processes?, Neurotoxicity Research, 7, (1,2) pp. 5-15. ISSN 1029-8428 (2005) [Refereed Article]

DOI: doi:10.1007/BF03033772


The precise role of β-amyloid plaque formation in the cascade of brain cell changes that lead to neurodegeneration and dementia in Alzheimer's disease has been unclear. Studies have indicated that neuronal processes surrounding and within plaques undergo a series of biochemical and morphological alterations. Morphological alterations include reactive, degenerative and sprouting-related 'dystrophic' neuritic structures, derived principally from axons, which involve specific changes in cytoskeletal proteins such as tau and NF triplet proteins. More compact and fibrous plaques are associated with more extensive neuritic pathology than non-fibrillar, diffuse β-amyloid deposits. Cortical apical dendritic processes are either 'clipped' by plaque formation or are bent around more compact plaques. Examination of cases of 'pathological' brain ageing, which may represent a preclinical form of Alzheimer's disease, demonstrated that the earliest neuritic pathology associated with plaques was similar to the reactive changes that follow structural injury to axons. In vivo and in vitro experimental models of structural injury to axons produce identical reactive changes that subsequently lead to an attempt at regenerative sprouting by damaged axons. Thus, β-amyloid plaque formation may cause structural injury to axons that is subsequently followed by an aberrant sprouting response that presages neurodegeneration and dementia. Identification of the key neuronal alterations underlying the pathology of Alzheimer's disease may provide new avenues for therapeutic intervention. © Springer 2005.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Other biological sciences
Research Field:Other biological sciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Woodhouse, A (Dr Adele Woodhouse)
UTAS Author:West, AK (Professor Adrian West)
UTAS Author:Chuckowree, JA (Dr Jyoti Chuckowree)
UTAS Author:Vickers, JC (Professor James Vickers)
UTAS Author:Dickson, TC (Professor Tracey Dickson)
ID Code:32824
Year Published:2005
Web of Science® Times Cited:20
Deposited By:Pathology
Deposited On:2005-08-01
Last Modified:2007-05-29

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