We and others have demonstrated that at least early in the disease process, inflammatory activation in the CNS can have positive disease modifying effects in mouse models of Alzheimer’s disease [33, 54, 58, 59]; similarly, in this study, we demonstrate that at least in an acute scenario, IL-6 induced innate immune activation can have a protective outcome in wild type mice following exogenous αSyn challenge. This evidence concerns the gene IL6 and early-onset autosomal dominant Alzheimer disease.