Microglial TNF and IL-1 as early disease-modifiers in Alzheimer's-like disease in mice

Laura Ilkjær, Alicia Babcock, Bente Finsen

    Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review


    In Alzheimer's disease (AD) signs of microglial activation is evident already in prodromal and early AD. This and other evidence suggest that neuroinflammation contributes to the progression of the early disease development in AD. Microglial cells have the capacity to produce cytokines such as TNF and IL-1, and to phagocytose and clear amyloid beta (As), however, the influence of TNF and IL-1, and inflammation in general, on these processes is still poorly understood. We have studied the development of As pathology, and basal and lipopolysaccharide (LPS) stimulated microglial cytokine production in the APPswe/PS1DE9 mouse model of AD. In these mice, cortical As plaque load shows a sigmoidal trajectory with age, as it does in AD. At 12 months of age, when As pathology is welldeveloped, TNF and IL-1s are produced in significantly higher proportions of microglia in the APPswe/PS1DE9 mice, than in wildtype mice. Microglial expression of TNF and IL-1s can be significantly increased by i.p. injection of LPS, which we find reduces cortical As pathology at 12 months. Results will also be reported on the influence of IL-1 in modulating As pathology during early disease stages in APPswe/PS1DE9 mice. Together, the presented work underscores the potential of microglia in modifying As pathology in early AD. Improving the clearance of As in prodromal and early AD, might delay or impede the development of AD.
    Udgave nummerS1
    Sider (fra-til)E52-E53
    StatusUdgivet - aug. 2015
    BegivenhedXII European Meeting on Glial Cell Function in Health and Disease - Bilbao, Spanien
    Varighed: 14. jul. 201518. jul. 2015


    KonferenceXII European Meeting on Glial Cell Function in Health and Disease


    • *glia cell *European *mouse *cell function *health pathology microglia wild type mouse inflammation disease course mouse model cytokine production nervous system inflammation injection Alzheimer disease *interleukin 1 lipopolysaccharide amyloid cytokine