TY - JOUR AU - Heneka, Michael AU - Carson, Monica J AU - El Khoury, Joseph AU - Landreth, Gary E AU - Brosseron, Frederic AU - Feinstein, Douglas L AU - Jacobs, Andreas H AU - Wyss-Coray, Tony AU - Vitorica, Javier AU - Ransohoff, Richard M AU - Herrup, Karl AU - Frautschy, Sally A AU - Finsen, Bente AU - Brown, Guy C AU - Verkhratsky, Alexei AU - Yamanaka, Koji AU - Koistinaho, Jari AU - Latz, Eicke AU - Halle, Annett AU - Petzold, Gabor C AU - Town, Terrence AU - Morgan, Dave AU - Shinohara, Mari L AU - Perry, V Hugh AU - Holmes, Clive AU - Bazan, Nicolas G AU - Brooks, David J AU - Hunot, Stéphane AU - Joseph, Bertrand AU - Deigendesch, Nikolaus AU - Garaschuk, Olga AU - Boddeke, Erik AU - Dinarello, Charles A AU - Breitner, John C AU - Cole, Greg M AU - Golenbock, Douglas T AU - Kummer, Markus P TI - Neuroinflammation in Alzheimer's disease. JO - The lancet / Neurology VL - 14 IS - 4 SN - 1474-4422 CY - London PB - Lancet Publ. Group M1 - DZNE-2020-04173 SP - 388-405 PY - 2015 AB - Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease. KW - Alzheimer Disease: genetics KW - Alzheimer Disease: immunology KW - Alzheimer Disease: metabolism KW - Alzheimer Disease: pathology KW - Alzheimer Disease: prevention & control KW - Animals KW - Anti-Inflammatory Agents, Non-Steroidal: therapeutic use KW - Astrocytes: immunology KW - Astrocytes: pathology KW - Biomarkers: blood KW - Biomarkers: cerebrospinal fluid KW - Brain Injuries: complications KW - Brain Injuries: metabolism KW - Clinical Trials as Topic KW - Disease Models, Animal KW - Disease Progression KW - Humans KW - Immunity, Innate KW - Immunization KW - Inflammation: diagnosis KW - Inflammation: immunology KW - Inflammation: metabolism KW - Inflammation Mediators: immunology KW - Inflammation Mediators: metabolism KW - Locus Coeruleus: pathology KW - Microglia: immunology KW - Microglia: pathology KW - Nootropic Agents: administration & dosage KW - Obesity: complications KW - Obesity: metabolism KW - Phagocytosis KW - Protein Folding KW - Risk Factors KW - Severity of Illness Index KW - Anti-Inflammatory Agents, Non-Steroidal (NLM Chemicals) KW - Biomarkers (NLM Chemicals) KW - Inflammation Mediators (NLM Chemicals) KW - Nootropic Agents (NLM Chemicals) LB - PUB:(DE-HGF)16 C6 - pmid:25792098 C2 - pmc:PMC5909703 DO - DOI:10.1016/S1474-4422(15)70016-5 UR - https://pub.dzne.de/record/137851 ER -