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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 Dickson
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.

History

Publication title

Acta Neuropathologica

Volume

119

Issue

5

Pagination

567-577

ISSN

0001-6322

Department/School

Menzies Institute for Medical Research

Publisher

Springer-Verlag

Place of publication

175 Fifth Ave, New York, USA, Ny, 10010

Rights statement

The original publication is available at www.springerlink.com

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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