Differential effects of apoE and apoJ mimetic peptides on the action of an anti-Aβ scFv in 3xTg-AD mice

Biochemical Pharmacology
Laia Montoliu-GayaSandra Villegas

Abstract

Anti-Aβ immunotherapy has emerged as a promising approach to treat Alzheimer's disease (AD). The single-chain variable fragment scFv-h3D6 is an anti-Aβ antibody fragment that lacks the Fc region, which is associated with the induction of microglial reactivity by the full-length monoclonal antibody bapineuzumab. ScFv-h3D6 was previously shown to restore the levels of apolipoprotein E (apoE) and apolipoprotein J (apoJ) in a triple-transgenic-AD (3xTg-AD) mouse model. Since apoE and apoJ play an important role in the development of AD, we aimed to study the in vivo effect of the combined therapy of scFv-h3D6 with apoE and apoJ mimetic peptides (MPs). Four-and-a-half-month-old 3xTg-AD mice were treated for six weeks with scFv-h3D6, apoE-MP, apoJ-MP, or a combination of scFv-h3D6 with each of the MPs, or a vehicle, and then the results were compared to non-transgenic mice. Magnetic Resonance Imaging showed a general tendency of the different treatments to protect against the reduction in brain volume. Aβ burden decreased after treatment with scFv-h3D6, apoE-MP, or apoJ-MP, but the effect was not as evident with the combined therapies. In terms of glial reactivity, apoE-MP showed a potent anti-inflammatory effect that was eased by th...Continue Reading

Citations

Sep 16, 2020·International Journal of Molecular Sciences·Alejandro R RodaSandra Villegas
Nov 17, 2020·Frontiers in Aging Neuroscience·Kriti ChaplotIris Lindberg
Jan 19, 2021·Journal of Alzheimer's Disease : JAD·Jessica L DennisonClaes Wahlestedt
Aug 13, 2021·Nature Communications·Patricia Yuste-ChecaF Ulrich Hartl

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