Both Amyloid-β Peptide and Tau Protein Are Affected by an Anti-Amyloid-β Antibody Fragment in Elderly 3xTg-AD Mice
Ramos Roda, Alejandro. (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Montoliu Gaya, Laia (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Serra-Mir, Gabriel (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Villegas Hernández, Sandra (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date:	2020
Abstract:	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.
Grants:	Ministerio de Economía y Competitividad SAF2017-89613-R
Note:	Altres ajuts: ARR received an FPU fellowship and GSM a PIF-UAB fellowship
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Aβ ; Tau ; Immunotherapy ; Alzheimer ; ScFv ; 3xTg-AD
Published in:	International journal of molecular sciences, Vol. 21, Núm. 18 (September 2020) , art. 6630, ISSN 1422-0067

DOI: 10.3390/ijms21186630
PMID: 32927795

23 p, 12.1 MB

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