Neuroimmune interactions in Alzheimer's disease-New frontier with old challenges?

The perceived role of the immune system in neurodegenerative diseases has undergone drastic changes over time. Initially considered as a passive bystander, then condemned as a mediator of neurodegeneration and now established as an important player in the pathogenetic cascade, neuroimmune interactions have come a long way to arrive center stage in Alzheimer's disease research. Despite major breakthroughs in recent years, basic questions remain unanswered as conflicting data describe immune overactivation, inadequate response or exhaustion of the immune system in neurodegenerative diseases. Furthermore, difficulties in translating in vitro and in vivo studies in model systems to the complex human disease condition with multiple overlapping pathologies and the long disease duration in patients suffering from neurodegenerative diseases have hampered progress. Development of novel, advanced model systems, as well as new technologies to interrogate existing disease models and valuable collections of human tissue samples, including brain tissue in parallel with improved imaging and biomarker technologies are guiding the way to better understand the role of the immune system in Alzheimer's disease with hopes for more effective interventions in the future.