| Autor: |
Wati, Henny, Kawarabayashi, Takeshi, Matsubara, Etsuro, Kasai, Ayumi, Hirasawa, Takae, Kubota, Takeo, Harigaya, Yasuo, Shoji, Mikio, Maeda, Shuichiro |
| Předmět: |
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| Zdroj: |
Brain Pathology; Jan2009, Vol. 19 Issue 1, p48-57, 10p, 2 Black and White Photographs, 2 Charts, 2 Graphs |
| Abstrakt: |
Transthyretin (TTR) binds amyloid-β (Aβ) and prevents Aβ 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 Aβ deposits, tau hyperphosphorylation and apoptosis. TTR is, therefore, speculated to prevent Aβ pathology in AD. However, a role for TTR in Aβ deposition is not yet known. To investigate the relationship between TTR and Aβ 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 Aβ 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 Aβ 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 Aβ deposition in the mouse model of AD. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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