Overview of immune system in AD

Abstract Background The accumulation of neurotoxic amyloid beta peptides along with neurofibrillary tangle formation are key pathological hallmarks of Alzheimer’s disease. The brain has been considered as an immune‐privileged organ, however, increasing evidence from translational, genetic, and pathological studies suggests that activation of distinct innate immune pathways are a third important disease hallmark which, once initiated, actively contributes to disease progression and chronicity. Method Representing the innate immune system, microglial cells play a pivotal role in this immune response and are activated by binding of aggregated proteins or aberrant nucleic acids to pattern recognition receptors. This immune activation leads to the release of inflammatory mediators, but also distracts microglia cells from their physiological functions and tasks, including debris clearance and trophic factor support. Likewise, the adaptive immune system shows changes that suggest that it actively contributes to the immune processes that are ongoing in the brain during the entire disease trajectory. Result Several lines of evidence suggest that immune processes may have protective as well as detrimental consequences. The precise molecular, spatial and temporal characterization of these immune processes will be necessary in order to develop new diagnostics as well as therapeutic interventions. Conclusion An overview of the current understanding of immune mechanisms in AD, their link to the microbiome, as well as open questions will be outlined and discussed.