Aβ peptide conformation determines uptake and interleukin-1α expression by primary microglial cells

Abstract 

Microglia clear amyloid beta (Aβ) after immunization. The interaction of Aβ with the microglial cell surface also results in cytokine expression. Soluble oligomers and protofibrils of Aβ may be more neurotoxic than Aβ fibrils. We investigated the effects of oligomeric, protofibrillar and fibrillar Aβ40 and Aβ42 peptides on uptake and IL-1α expression by primary microglia. Aβ peptide assemblies were extensively characterized. Primary microglial cells were exposed to different Aβ40 and Aβ42 assemblies and IL-1α expression was quantified. To study uptake, microglial cells were exposed to different assemblies of Cy3-labeled Aβ. We found that Aβ42 and Aβ40 oligomers and fibrils induced IL-1α expression, but protofibrils did not. We also observed that all forms of Aβ42 (oligomer, protofibril and fibril) and Aβ40 fibrils were taken up by the microglial cells. These results demonstrate that microglial cells can take up non-fibrillar Aβ and that oligomeric peptide induces an inflammatory response. The uptake of oligomeric and protofibrillar Aβ by microglia merits further investigation as a potential means for removing these neurotoxic species from the brain.

Keywords: Microglia, Phagocytosis, IL-1α, Amyloid beta, Oligomer, Alzheimer's disease