Both Amyloid-β Peptide and Tau Protein Are Affected by an Anti-Amyloid-β Antibody Fragment in Elderly 3xTg-AD Mice
Alzheimer's disease (AD) is the most common dementia worldwide. According to the amyloid hypothesis,the early accumulation of the Aβ-peptide triggers tau phosphorylation,synaptic dysfunction, and eventually neuronal death leading to cognitive impairment, as well as behavioral and psychological...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:233191 |
| Acceso en línea: | https://ddd.uab.cat/record/233191 https://dx.doi.org/urn:doi:10.3390/ijms21186630 |
| Access Level: | acceso abierto |
| Palabra clave: | Aβ Tau Immunotherapy Alzheimer ScFv 3xTg-AD |
| Sumario: | Alzheimer's disease (AD) is the most common dementia worldwide. According to the amyloid hypothesis,the early accumulation of the Aβ-peptide triggers tau phosphorylation,synaptic dysfunction, and eventually neuronal death leading to cognitive impairment, as well as behavioral and psychological symptoms of dementia. ScFv-h3D6 is a single-chain variable fragment that has already shown its ability to diminish the amyloid burden in 5-month-old 3xTg-AD mice. However, tau pathology is not evident at this early stage of the disease in this mouse model. In this study, the effects of scFv-h3D6 on Aβ and tau pathologies have been assessed in 22-month-old 3xTg-AD mice. Briefly, 3xTg-AD female mice were treated for 2 weeks with scFv-h3D6 and compared with 3xTg-AD and non-transgenic (NTg) mice treated with PBS. The treatment with scFv-h3D6 was unequivocally effective in reducing the area of Aβ staining. Furthermore, a tendency for a reduction in tau levels was also observed after treatment that points to the interplay between Aβ and tau pathologies. The pro-inflammatory state observed in the 3xTg-AD mice did not progress after scFv-h3D6 treatment. In addition, the treatment did not alter the levels of apolipoprotein E or apolipoprotein J. Thus, a 2-week treatment with scFv-h3D6 was able to reduce AD-like pathology in elderly 3xTg-AD female mice. |
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