Focal demyelination in Alzheimer's disease and transgenic mouse models.
We have investigated alterations in myelin associated with Abeta 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 Abeta 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 Abeta plaques. Furthermore, we found a focal loss of oligodendrocytes in sporadic and preclinical AD cases associated with Abeta 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.
Mitew
Stanislaw
S
NeuroRepair Group, Wicking Dementia Research and Education Centre, Menzies Research Institute, University of Tasmania, Hobart, TAS 7000, Australia.
Kirkcaldie
Matthew T K
MT
Halliday
Glenda M
GM
Shepherd
Claire E
CE
Vickers
James C
JC
Dickson
Tracey C
TC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D019579:Neocortex / Q000378:metabolism / Q000473:pathology*; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics
D016229:Amyloid beta-Peptides; D053764:Presenilin-1