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Possible involvement of transthyretin in hippocampal beta-amyloid burden and learning behaviors in a mouse model of Alzheimer's disease (TgCRND8).
Neurodegener Dis 2010; 7(1-3):88-95ND

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+Show Affiliations

Douglas Mental Health University Institute and Department of Psychiatry, McGill University, Montreal, Que., Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20173334

Citation

Doggui, Sihem, et al. "Possible Involvement of Transthyretin in Hippocampal Beta-amyloid Burden and Learning Behaviors in a Mouse Model of Alzheimer's Disease (TgCRND8)." Neuro-degenerative Diseases, vol. 7, no. 1-3, 2010, pp. 88-95.
Doggui S, Brouillette J, Chabot JG, et al. Possible involvement of transthyretin in hippocampal beta-amyloid burden and learning behaviors in a mouse model of Alzheimer's disease (TgCRND8). Neurodegener Dis. 2010;7(1-3):88-95.
Doggui, S., Brouillette, J., Chabot, J. G., Farso, M., & Quirion, R. (2010). Possible involvement of transthyretin in hippocampal beta-amyloid burden and learning behaviors in a mouse model of Alzheimer's disease (TgCRND8). Neuro-degenerative Diseases, 7(1-3), pp. 88-95. doi:10.1159/000285513.
Doggui S, et al. Possible Involvement of Transthyretin in Hippocampal Beta-amyloid Burden and Learning Behaviors in a Mouse Model of Alzheimer's Disease (TgCRND8). Neurodegener Dis. 2010;7(1-3):88-95. PubMed PMID: 20173334.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Possible involvement of transthyretin in hippocampal beta-amyloid burden and learning behaviors in a mouse model of Alzheimer's disease (TgCRND8). AU - Doggui,Sihem, AU - Brouillette,Jonathan, AU - Chabot,Jean-Guy, AU - Farso,Mark, AU - Quirion,Rémi, Y1 - 2010/02/18/ PY - 2010/2/23/entrez PY - 2010/2/23/pubmed PY - 2010/7/22/medline SP - 88 EP - 95 JF - Neuro-degenerative diseases JO - Neurodegener Dis VL - 7 IS - 1-3 N2 - 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. SN - 1660-2862 UR - https://www.unboundmedicine.com/medline/citation/20173334/Possible_involvement_of_transthyretin_in_hippocampal_beta_amyloid_burden_and_learning_behaviors_in_a_mouse_model_of_Alzheimer's_disease__TgCRND8__ L2 - https://www.karger.com?DOI=10.1159/000285513 DB - PRIME DP - Unbound Medicine ER -