Possible involvement of transthyretin in hippocampal beta-amyloid burden and learning behaviors in a mouse model of Alzheimer's disease (TgCRND8).

Abstract

BACKGROUND:

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss, possibly triggered by the accumulation of beta-amyloid (Abeta) peptides and the hyperphosphorylation of Tau neurofilament protein. Recent findings have shown that transthyretin (TTR) is a potent scavenger of Abeta 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 Abeta deposition, we crossed mouse carrying a deletion of TTR (TTR(- or -)) with a transgenic mouse model of AD (TgCRND8), and Abeta burden and spatial learning capacities were evaluated at 4 and 6 months of age (exclusion of the 6 month-old TgCRND8/TTR(- or -) group due to low survival rate).

RESULTS:

Rather surprisingly, Abeta plaque burden was significantly reduced in the hippocampus of 4-month-old TgCRND8/TTR(+ or -), and to a lesser extent in TgCRND8/TTR(- or -), as compared to age-matched TgCRND8/TTR(+ or +). 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 Abeta 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.

• Authors: Sihem Doggui, Jonathan Brouillette, Jean-Guy Chabot, Mark Farso, Rémi Quirion
• Journal: Neuro-degenerative diseases (Neurodegener Dis) Vol. 7 Issue 1-3 Pg. 88-95 ( 2010) ISSN: 1660-2862 [Electronic] Switzerland
• PMID: 20173334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 S. Karger AG, Basel.

Chemical References

• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Prealbumin

Topics

• Age Factors
• Alzheimer Disease (complications, metabolism, pathology)
• Amyloid beta-Peptides (genetics, metabolism)
• Amyloid beta-Protein Precursor (genetics)
• Animals
• Disease Models, Animal
• Hippocampus (metabolism)
• Learning Disabilities (etiology)
• Maze Learning (physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Prealbumin (deficiency, metabolism)