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Focal demyelination in Alzheimer's disease and transgenic mouse models
journal contribution
posted on 2023-05-17, 02:46 authored by Mitew, S, Matthew KirkcaldieMatthew Kirkcaldie, Halliday, G, Shepherd, CE, James VickersJames Vickers, Tracey DicksonTracey DicksonWe 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.
History
Publication title
Acta NeuropathologicaVolume
119Issue
5Pagination
567-577ISSN
0001-6322Department/School
Menzies Institute for Medical ResearchPublisher
Springer-VerlagPlace of publication
175 Fifth Ave, New York, USA, Ny, 10010Rights statement
The original publication is available at www.springerlink.comRepository Status
- Restricted