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Focal demyelination in Alzheimer's disease and transgenic mouse models

Citation

Mitew, S and Kirkcaldie, MTK and Halliday, G and Shepherd, CE and Vickers, JC and Dickson, TC, Focal demyelination in Alzheimer's disease and transgenic mouse models, Acta Neuropathologica, 119, (5) pp. 567-577. ISSN 0001-6322 (2010) [Refereed Article]


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The original publication is available at www.springerlink.com

DOI: doi:10.1007/s00401-010-0657-2

Abstract

We have investigated alterations in myelin associated with Ab plaques, a major pathological hallmark of Alzheimer’s disease (AD), in human tissue and relevant transgenic mice models. Using quantitative morphological techniques, we determined that fibrillar Ab pathology in the grey matter of the neocortex was associated with focal demyelination in human presenilin-1 familial, sporadic and preclinical AD cases, as well as in two mouse transgenic models of AD, compared with age-matched control tissue. This demyelination was most pronounced at the core of Ab plaques. Furthermore, we found a focal loss of oligodendrocytes in sporadic and preclinical AD cases associated with Ab plaque cores. In human and transgenic mice alike, plaque-free neocortical regions showed no significant demyelination or oligodendrocyte loss compared with controls. Dystrophic neurites associated with the plaques were also demyelinated. We suggest that such plaque-associated focal demyelination of the cortical grey matter might impair cortical processing, and may also be associated with aberrant axonal sprouting that underlies dystrophic neurite formation.

Item Details

Item Type:Refereed Article
Keywords:Dystrophic neurites; Demyelination; Abeta plaques; Degeneration; Alzheimer’s disease
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Mitew, S (Mr Stanislaw Mitew)
Author:Kirkcaldie, MTK (Dr Matthew Kirkcaldie)
Author:Vickers, JC (Professor James Vickers)
Author:Dickson, TC (Professor Tracey Dickson)
ID Code:64012
Year Published:2010
Web of Science® Times Cited:47
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-06-16
Last Modified:2013-07-16
Downloads:2 View Download Statistics

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