Modulation of the Immunoproteasome Affects Pathological Tau Aggregation in Alzheimer’s Disease

Abstract

AbstractBackgroundThe Immunoproteasome is a dynamic system found in microglia that is induced under inflammatory conditions and previously hypothesized to be causative of neurodegenerative disorders like Alzheimer’s Disease.MethodMice with immunoproteasome deficiency (LMPPS) and mice with intact immunoproteasome (PS19) were analyzed for AD progression through total tau aggregation and microglia activity. Primary microglia were extracted from normal and LMPKO mouse strains and their total engulfment of tau‐aggregate containing cells were compared.ResultLMPPS mice had significantly higher mean aggregation of tau compared to PS19 mice. LMPPS mice also showed a significantly increased activation of microglia and a slightly increased number of total microglia compared to PS19 mice. In‐vitro results showed increased total engulfment of tau‐aggregate containing cells for LMPKO microglia but statistically insignificant difference when comparing proportion of engulfing microglia.ConclusionTo our knowledge, our results are the first to show that the immunoproteasome is neuroprotective against tauopathies like Alzheimer’s Disease in mice.