Aβ-oligomer uptake and the resulting inflammatory response in adult human astrocytes are precluded by an anti-Aβ single chain variable fragment in combination with an apoE mimetic peptide

Proposed mechanism of action of apoE and apoJ mimetic peptides (MP) and a single chain variable fragment of a humanized monoclonal antibody that specifically detects Amyloid-β (Aβ), scFv-h3D6, on Aβ clearance and Aβ-induced inflammation in adult human primary astrocytes. Aβ oligomers induce the release of proinflammatory cytokines IL-6 and MCP-1, which is reduced in the presence of apoE-MP in vitro. At the same time, Aβ oligomer uptake is reduced by apoE-MP, as well as apoJ-MP and, more potently, scFv-h3D6. Because apo-MP do not interfere with the inhibitory effect of scFv-h3D6 on uptake, a combination of the anti-inflammatory apoE-MP and scFv-h3D6 merits further investigation for therapeutic use.120