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- Title
Possible Involvement of Transthyretin in Hippocampal β-Amyloid Burden and Learning Behaviors in a Mouse Model of Alzheimer’s Disease (TgCRND8).
- Authors
Doggui, Sihem; Brouillette, Jonathan; Chabot, Jean-Guy; Farso, Mark; Quirion, Rémi
- Abstract
Background: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive memory loss, possibly triggered by the accumulation of β-amyloid (Aβ) peptides and the hyperphosphorylation of Tau neurofilament protein. Recent findings have shown that transthyretin (TTR) is a potent scavenger of Aβ peptide deposits, suggesting a possible neuroprotective role for TTR in neurodegenerative processes associated with amyloidogenesis, such as AD. Methods: To investigate the relationship between TTR and Aβ deposition, we crossed mouse carrying a deletion of TTR (TTR–/–) with a transgenic mouse model of AD (TgCRND8), and Aβ burden and spatial learning capacities were evaluated at 4 and 6 months of age (exclusion of the 6 month-old TgCRND8/TTR–/– group due to low survival rate). Results: Rather surprisingly, Aβ plaque burden was significantly reduced in the hippocampus of 4-month-old TgCRND8/TTR+/–, and to a lesser extent in TgCRND8/TTR–/–, as compared to age-matched TgCRND8/TTR+/+. No difference in plaque burden was found between any groups in 6-month-old animals. At 4 and 6 months of age, all populations of these hybrid transgenic mice displayed similar magnitude of spatial memory deficits in the Morris water maze task. Conclusion: Since TgCRND8 mice represent an aggressive model of Aβ deposition with plaques developing as early as 3 months of age, along with spatial learning deficits, it may be already too late at 4 and 6 months of age to observe significant changes due to the deletion of the TTR gene. Copyright © 2010 S. Karger AG, Basel
- Subjects
ALZHEIMER'S disease; NEURODEGENERATION; TRANSTHYRETIN; HIPPOCAMPUS (Brain); ANIMAL models in research
- Publication
Neurodegenerative Diseases, 2010, Vol 7, Issue 1-3, p88
- ISSN
1660-2854
- Publication type
Article
- DOI
10.1159/000285513