Tags

Type your tag names separated by a space and hit enter

A novel transgenic rat model with a full Alzheimer's-like amyloid pathology displays pre-plaque intracellular amyloid-beta-associated cognitive impairment.
J Alzheimers Dis. 2010; 20(1):113-26.JA

Abstract

Alzheimer's disease (AD) is a neurodegenerative pathology in which amyloid-beta (Abeta) peptide accumulates in different brain areas leading to deposition of plaques and a progressive decline of cognitive functions. After a decade in which a number of transgenic (Tg) mouse models mimicking AD-like amyloid-deposition pathology have been successfully generated, few rat models have been reported that develop intracellular and extracellular Abeta accumulation, together with impairment of cognition. The generation of a Tg rat reproducing the full AD-like amyloid pathology has been elusive. Here we describe the generation and characterization of a new transgenic rat line, coded McGill-R-Thy1-APP, developed to express the human amyloid-beta precursor protein (AbetaPP) carrying both the Swedish and Indiana mutations under the control of the murine Thy1.2 promoter. The selected mono-transgenic line displays an extended phase of intraneuronal Abeta accumulation, already apparent at 1 week after birth, which is widespread throughout different cortical areas and the hippocampus (CA1, CA2, CA3, and dentate gyrus). Homozygous Tg animals eventually produce extracellular Abeta deposits and, by 6 months of age, dense, thioflavine S-positive, amyloid plaques are detected, associated with glial activation and surrounding dystrophic neurites. The cognitive functions in transgenic McGill-R-Thy1-APP rats, as assessed using the Morris water maze task, were found already altered as early as at 3 months of age, when no CNS plaques are yet present. The spatial cognitive impairment becomes more prominent in older animals (13 months), where the behavioral performance of Tg rats positively correlates with the levels of soluble Abeta (trimers) measured in the cortex.

Authors+Show Affiliations

Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

20164597

Citation

Leon, Wanda Carolina, et al. "A Novel Transgenic Rat Model With a Full Alzheimer's-like Amyloid Pathology Displays Pre-plaque Intracellular Amyloid-beta-associated Cognitive Impairment." Journal of Alzheimer's Disease : JAD, vol. 20, no. 1, 2010, pp. 113-26.
Leon WC, Canneva F, Partridge V, et al. A novel transgenic rat model with a full Alzheimer's-like amyloid pathology displays pre-plaque intracellular amyloid-beta-associated cognitive impairment. J Alzheimers Dis. 2010;20(1):113-26.
Leon, W. C., Canneva, F., Partridge, V., Allard, S., Ferretti, M. T., DeWilde, A., Vercauteren, F., Atifeh, R., Ducatenzeiler, A., Klein, W., Szyf, M., Alhonen, L., & Cuello, A. C. (2010). A novel transgenic rat model with a full Alzheimer's-like amyloid pathology displays pre-plaque intracellular amyloid-beta-associated cognitive impairment. Journal of Alzheimer's Disease : JAD, 20(1), 113-26. https://doi.org/10.3233/JAD-2010-1349
Leon WC, et al. A Novel Transgenic Rat Model With a Full Alzheimer's-like Amyloid Pathology Displays Pre-plaque Intracellular Amyloid-beta-associated Cognitive Impairment. J Alzheimers Dis. 2010;20(1):113-26. PubMed PMID: 20164597.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel transgenic rat model with a full Alzheimer's-like amyloid pathology displays pre-plaque intracellular amyloid-beta-associated cognitive impairment. AU - Leon,Wanda Carolina, AU - Canneva,Fabio, AU - Partridge,Vanessa, AU - Allard,Simon, AU - Ferretti,Maria Teresa, AU - DeWilde,Arald, AU - Vercauteren,Freya, AU - Atifeh,Ramtin, AU - Ducatenzeiler,Adriana, AU - Klein,William, AU - Szyf,Moshe, AU - Alhonen,Leena, AU - Cuello,A Claudio, PY - 2010/2/19/entrez PY - 2010/2/19/pubmed PY - 2010/7/9/medline SP - 113 EP - 26 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 20 IS - 1 N2 - Alzheimer's disease (AD) is a neurodegenerative pathology in which amyloid-beta (Abeta) peptide accumulates in different brain areas leading to deposition of plaques and a progressive decline of cognitive functions. After a decade in which a number of transgenic (Tg) mouse models mimicking AD-like amyloid-deposition pathology have been successfully generated, few rat models have been reported that develop intracellular and extracellular Abeta accumulation, together with impairment of cognition. The generation of a Tg rat reproducing the full AD-like amyloid pathology has been elusive. Here we describe the generation and characterization of a new transgenic rat line, coded McGill-R-Thy1-APP, developed to express the human amyloid-beta precursor protein (AbetaPP) carrying both the Swedish and Indiana mutations under the control of the murine Thy1.2 promoter. The selected mono-transgenic line displays an extended phase of intraneuronal Abeta accumulation, already apparent at 1 week after birth, which is widespread throughout different cortical areas and the hippocampus (CA1, CA2, CA3, and dentate gyrus). Homozygous Tg animals eventually produce extracellular Abeta deposits and, by 6 months of age, dense, thioflavine S-positive, amyloid plaques are detected, associated with glial activation and surrounding dystrophic neurites. The cognitive functions in transgenic McGill-R-Thy1-APP rats, as assessed using the Morris water maze task, were found already altered as early as at 3 months of age, when no CNS plaques are yet present. The spatial cognitive impairment becomes more prominent in older animals (13 months), where the behavioral performance of Tg rats positively correlates with the levels of soluble Abeta (trimers) measured in the cortex. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/20164597/A_novel_transgenic_rat_model_with_a_full_Alzheimer's_like_amyloid_pathology_displays_pre_plaque_intracellular_amyloid_beta_associated_cognitive_impairment_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-2010-1349 DB - PRIME DP - Unbound Medicine ER -