Triple-transgenic Alzheimer's disease mice exhibit region-specific abnormalities in brain myelination patterns prior to appearance of amyloid and tau pathology

Alzheimer's disease (AD) is a progressively debilitating brain disorder pathologically defined by extracellular amyloid plaques, intraneuronal neurofibrillary tangles, and synaptic disintegrity. AD has not been widely considered a disease of white matter, but more recent evidence suggests the e...

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Bibliographic Details
Published in:Glia 2009-01, Vol.57 (1), p.54-65
Main Authors: Desai, Maya K., Sudol, Kelly L., Janelsins, Michelle C., Mastrangelo, Michael A., Frazer, Maria E., Bowers, William J.
Format: Article
Language:English
Subjects:
3xTg-AD
Age Factors
Alzheimer Disease - genetics
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Animals
Brain - metabolism
Brain - pathology
Brain - ultrastructure
CNPase
electron microscopy
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
myelin
myelin basic protein
Myelin Sheath - genetics
Myelin Sheath - pathology
Myelin Sheath - ultrastructure
Nerve Fibers, Myelinated - metabolism
Nerve Fibers, Myelinated - pathology
Nerve Fibers, Myelinated - ultrastructure
oligodendrocyte
Plaque, Amyloid - genetics
Plaque, Amyloid - pathology
Plaque, Amyloid - ultrastructure
tau Proteins - genetics
tau Proteins - metabolism
tau Proteins - ultrastructure
Tauopathies - genetics
Tauopathies - metabolism
Tauopathies - pathology
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Summary:Alzheimer's disease (AD) is a progressively debilitating brain disorder pathologically defined by extracellular amyloid plaques, intraneuronal neurofibrillary tangles, and synaptic disintegrity. AD has not been widely considered a disease of white matter, but more recent evidence suggests the existence of abnormalities in myelination patterns and myelin attrition in AD‐afflicted human brains. Herein, we demonstrate that triple‐transgenic AD (3xTg‐AD) mice, which harbor the human amyloid precursor protein Swedish mutant transgene, presenilin knock‐in mutation, and tau P301L mutant transgene, exhibit significant region‐specific alterations in myelination patterns and in oligodendrocyte marker expression profiles at time points preceding the appearance of amyloid and tau pathology. These immunohistochemical signatures are coincident with age‐related alterations in axonal and myelin sheath ultrastructure as visualized by comparative electron microscopic examination of 3xTg‐AD and nontransgenic mouse brain tissue. Overall, these findings indicate that 3xTg‐AD mice represent a viable model in which to examine mechanisms underlying AD‐related myelination and neural transmission defects that occur early during presymptomatic stages of the disease process. © 2008 Wiley‐Liss, Inc.
ISSN:0894-1491
1098-1136
DOI:10.1002/glia.20734