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.
Highlights
Alzheimer’s disease (AD) is the most common cause of dementia worldwide
Previous studies have shown that anti-Aβ antibodies were mainly accumulated in the central periventricular areas, especially in the hippocampus of AD mouse models, where Aβ load is high [28]
ScFv-h3D6 co-localized with Aβ, in the extracellular plaques of the hippocampus and, and more intensely, inside the cornus amonis 3 (CA3) neurons (Figure 1A, arrows)
Summary
Alzheimer’s disease (AD) is the most common cause of dementia worldwide. Alzheimer’s International (ADI) estimated that more than 50 million people are suffering dementia worldwide nowadays and that the global economic cost of dementia for the year 2018 was above US$ 1 trillion [1]. Incidence rates of any dementia and AD are reported to be greater in women than men [2]. The incidence rate of AD in Europe was 11.08 per 1000 person-years; 13.25 per 1000 person-years in women, and 7.02 per 1000 person-years in men [3]. The prevalence of AD was 7.13% in women and 3.31% in men (overall, 5.05%). Because the prevalence of AD is estimated to be tripled in 30 years, the finding of disease-modifying drugs is mandatory
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