Heneka Michael T, Carson Monica J, El Khoury Joseph, Landreth Gary E, Brosseron Frederic, Feinstein Douglas L, Jacobs Andreas H, Wyss-Coray Tony, Vitorica Javier, Ransohoff Richard M, Herrup Karl, Frautschy Sally A, Finsen Bente, Brown Guy C, Verkhratsky Alexei, Yamanaka Koji, Koistinaho Jari, Latz Eicke, Halle Annett, Petzold Gabor C, Town Terrence, Morgan Dave, Shinohara Mari L, Perry V Hugh, Holmes Clive, Bazan Nicolas G, Brooks David J, Hunot Stéphane, Joseph Bertrand, Deigendesch Nikolaus, Garaschuk Olga, Boddeke Erik, Dinarello Charles A, Breitner John C, Cole Greg M, Golenbock Douglas T, Kummer Markus P
Department of Neurology, University Hospital Bonn, University of Bonn, Bonn, Germany; German Center for Neurodegnerative Diseases (DZNE), Bonn, Germany.
Division of Biomedical Sciences, Center for Glial-Neuronal Interactions, University of California, Riverside, CA, USA.
Lancet Neurol. 2015 Apr;14(4):388-405. doi: 10.1016/S1474-4422(15)70016-5.
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.
越来越多的证据表明，阿尔茨海默病的发病机制并不局限于神经元部分，而是包括与大脑免疫机制的强烈相互作用。错误折叠和聚集的蛋白质与小胶质细胞和星形胶质细胞上的模式识别受体结合，并引发以炎症介质释放为特征的先天性免疫反应，这有助于疾病的进展和严重程度。全基因组分析表明，几个增加散发性阿尔茨海默病风险的基因编码调节错误折叠蛋白质的胶质清除和炎症反应的因子。包括全身炎症和肥胖在内的外部因素可能会干扰大脑的免疫过程，并进一步促进疾病进展。对风险因素的调节以及针对这些免疫机制可能会带来未来治疗或预防阿尔茨海默病的策略。
