Focal demyelination in Alzheimer’s disease and transgenic mouse models
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We have investigated alterations in myelin associated with Aβ 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 Aβ 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 Aβ plaques. Furthermore, we found a focal loss of oligodendrocytes in sporadic and preclinical AD cases associated with Aβ 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.
KeywordsDystrophic neurites Demyelination Aβ plaques Degeneration Alzheimer’s disease
This work was funded by the Australian National Health and Medical Research Council and the J.O. and J.R. Wicking Trust (ANZ Charitable Services). The PS-1 human familial AD cases were provided by the Prince of Wales Medical Research Institute Tissue Resource Centre which is funded through an enabling grant from the Australian National Health and Medical Research Council. We thank Professor Poul H Jensen for providing the rabbit anti p25α antibody.
Conflict of interest statement
The authors declare that they have no conflict of interest.
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