| First Author | Desai MK | Year | 2009 |
| Journal | Glia | Volume | 57 |
| Issue | 1 | Pages | 54-65 |
| PubMed ID | 18661556 | Mgi Jnum | J:156225 |
| Mgi Id | MGI:4419073 | Doi | 10.1002/glia.20734 |
| Citation | Desai MK, et al. (2009) Triple-transgenic Alzheimer's disease mice exhibit region-specific abnormalities in brain myelination patterns prior to appearance of amyloid and tau pathology. Glia 57(1):54-65 |
| abstractText | 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. |
