Both Amyloid-? Peptide and Tau Protein Are Affected by an Anti-Amyloid-? Antibody Fragment in Elderly 3xTg-AD Mice.

ABSTRACT: Alzheimer's disease (AD) is the most common dementia worldwide. According to the amyloid hypothesis, the early accumulation of the A?-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 A? 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 A? staining. Furthermore, a tendency for a reduction in tau levels was also observed after treatment that points to the interplay between A? 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.

SUBMITTER: Roda AR 

PROVIDER: S-EPMC7554787 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature