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• W1977314215 abstract "Recently, our group and others have identified naturally occurring autoantibodies against Aß (nAbs-Aß) which are significantly reduced in patients suffering from Alzheimer's disease (AD). In AD, it is assumed that nAbs-Aß play a major role in clearing Aß. To date, not much is known about the interaction between nAbs-Aß and amyloid. MTT assays were performed to quantify cell viability following treatment of primary microglia with Aß and nAbs-Aß. FACS analysis was used to measure phagocytosis of primary microglia cells in response to treatment with Aß and nAbs-Aß. We used ELISA to analyse variations in cytokine concentrations. Western-blot/dot-blot techniques were used to show the interaction of nAbs-Aß with Aß-oligomers as well as to measure apoptosis. We were able to show that cytokine concentrations in primary microglia are significantly increased in response to treatment of cells with both Aß and nAbs-Aß. In particular, we observe an increase in TNF-a and IL-6 in primary microglia. It is known that Aß is toxic to cells, especially in oligomeric forms. Stimulation of primary microglia with Aß lead to cell death, which was partially reduced by pretreating Aß with nAbs-Aß. As oligomers are considered as the toxic peptides in Alzheimer's disease, we evaluated the interaction of nAbs-Aß with Aß oligomers. We can clearly demonstrate that addition of nAbs-Aß leads to a reduction in oligomer formation. In summary, we provide evidence that nAbs-Aß are able to breakdown toxic oligomers. Taking into account the peripheral sink hypothesis, breakdown of toxic oligomers may lead to a drain of Aß from the CSF to the peripheral blood, leading to a reduction in oligomer load. Interestingly, we observe a further increase in the concentration of IL-6 and TNF-α in response to treatment with Aß and nAbs-Aß. This may point to a stimulatory action of nAbs towards inflammatory cells and maybe result in increased removal of Aß. In addition, there is a decrease in toxicity in response to treatment with nAbs." @default.
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• W1977314215 date "2011-07-01" @default.
• W1977314215 modified "2023-09-27" @default.
• W1977314215 title "P2-459: In-vitro mechanisms of action of naturally occurring autoantibodies against Aβ" @default.
• W1977314215 doi "https://doi.org/10.1016/j.jalz.2011.05.1331" @default.
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