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Transthyretin accelerates vascular Abeta deposition in a mouse model of Alzheimer's disease.
Brain Pathol 2009; 19(1):48-57BP

Abstract

Transthyretin (TTR) binds amyloid-beta (Abeta) and prevents Abeta fibril formation in vitro. It was reported that the lack of neurodegeneration in a transgenic mouse model of Alzheimer's disease (AD) (Tg2576 mouse) was associated with increased TTR level in the hippocampus, and that chronic infusion of anti-TTR antibody into the hippocampus of Tg2576 mice led to increased local Abeta deposits, tau hyperphosphorylation and apoptosis. TTR is, therefore, speculated to prevent Abeta pathology in AD. However, a role for TTR in Abeta deposition is not yet known. To investigate the relationship between TTR and Abeta deposition, we generated a mouse line carrying a null mutation at the endogenous TTR locus and the human mutant amyloid precursor protein cDNA responsible for familial AD (Tg2576/TTR(-/-) mouse) by crossing Tg2576 mice with TTR-deficient mice. We asked whether Abeta deposition was accelerated in Tg2576/TTR(-/-) mice relative to the heterozygous mutant Tg2576 (Tg2576/TTR(+/-)) mice. Contrary to our expectations, the degree of total and vascular Abeta burdens in the aged Tg2576/TTR(-/-) mice was significantly reduced relative to the age-matched Tg2576/TTR(+/-) mice. Our experiments present, for the first time, compelling evidence that TTR does not suppress but rather accelerates vascular Abeta deposition in the mouse model of AD.

Authors+Show Affiliations

Department of Biochemistry, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan.No 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

18429966

Citation

Wati, Henny, et al. "Transthyretin Accelerates Vascular Abeta Deposition in a Mouse Model of Alzheimer's Disease." Brain Pathology (Zurich, Switzerland), vol. 19, no. 1, 2009, pp. 48-57.
Wati H, Kawarabayashi T, Matsubara E, et al. Transthyretin accelerates vascular Abeta deposition in a mouse model of Alzheimer's disease. Brain Pathol. 2009;19(1):48-57.
Wati, H., Kawarabayashi, T., Matsubara, E., Kasai, A., Hirasawa, T., Kubota, T., ... Maeda, S. (2009). Transthyretin accelerates vascular Abeta deposition in a mouse model of Alzheimer's disease. Brain Pathology (Zurich, Switzerland), 19(1), pp. 48-57. doi:10.1111/j.1750-3639.2008.00166.x.
Wati H, et al. Transthyretin Accelerates Vascular Abeta Deposition in a Mouse Model of Alzheimer's Disease. Brain Pathol. 2009;19(1):48-57. PubMed PMID: 18429966.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transthyretin accelerates vascular Abeta deposition in a mouse model of Alzheimer's disease. AU - Wati,Henny, AU - Kawarabayashi,Takeshi, AU - Matsubara,Etsuro, AU - Kasai,Ayumi, AU - Hirasawa,Takae, AU - Kubota,Takeo, AU - Harigaya,Yasuo, AU - Shoji,Mikio, AU - Maeda,Shuichiro, Y1 - 2008/04/22/ PY - 2008/4/24/entrez PY - 2008/4/24/pubmed PY - 2009/2/20/medline SP - 48 EP - 57 JF - Brain pathology (Zurich, Switzerland) JO - Brain Pathol. VL - 19 IS - 1 N2 - Transthyretin (TTR) binds amyloid-beta (Abeta) and prevents Abeta fibril formation in vitro. It was reported that the lack of neurodegeneration in a transgenic mouse model of Alzheimer's disease (AD) (Tg2576 mouse) was associated with increased TTR level in the hippocampus, and that chronic infusion of anti-TTR antibody into the hippocampus of Tg2576 mice led to increased local Abeta deposits, tau hyperphosphorylation and apoptosis. TTR is, therefore, speculated to prevent Abeta pathology in AD. However, a role for TTR in Abeta deposition is not yet known. To investigate the relationship between TTR and Abeta deposition, we generated a mouse line carrying a null mutation at the endogenous TTR locus and the human mutant amyloid precursor protein cDNA responsible for familial AD (Tg2576/TTR(-/-) mouse) by crossing Tg2576 mice with TTR-deficient mice. We asked whether Abeta deposition was accelerated in Tg2576/TTR(-/-) mice relative to the heterozygous mutant Tg2576 (Tg2576/TTR(+/-)) mice. Contrary to our expectations, the degree of total and vascular Abeta burdens in the aged Tg2576/TTR(-/-) mice was significantly reduced relative to the age-matched Tg2576/TTR(+/-) mice. Our experiments present, for the first time, compelling evidence that TTR does not suppress but rather accelerates vascular Abeta deposition in the mouse model of AD. SN - 1750-3639 UR - https://www.unboundmedicine.com/medline/citation/18429966/Transthyretin_accelerates_vascular_Abeta_deposition_in_a_mouse_model_of_Alzheimer's_disease_ L2 - https://doi.org/10.1111/j.1750-3639.2008.00166.x DB - PRIME DP - Unbound Medicine ER -