Alzheimer’s disease has an inflammatory component that is characterized by upregulation of proinflammatory cytokines, particularly in response to amyloid-beta (Aβ). Using a mouse model of Alzheimer’s disease, the authors of this study found increased production of the common interleukin-12 (IL-12) and IL-23 subunit p40 by microglia. Genetic ablation of p40 resulted in decreased cerebral amyloid load. Similar but smaller effects were observed with p35 or p19. Peripheral administration of a neutralizing p40-specific antibody likewise resulted in a reduction of cerebral amyloid load in mice. Intracerebroventricular delivery of p40 antibodies reduced the concentration of soluble Aβ and reversed cognitive deficits in aged mice. The concentration of p40 is also observed to be increased in the cerebrospinal fluid of human subjects with Alzheimer’s disease. The authors suggest that inhibition of the IL-12/IL-23 pathway may attenuate Alzheimer’s disease pathology and cognitive deficits.
Vom Berg J, Prokop S, Miller KR,Obst J, Kälin RE, Lopategui-Cabezas I, Wegner A, Mair F, Schipke CG, Peters O, Winter Y, Becher B, Heppner FL: Inhibition of IL-12/IL-23 signaling reduces Alzheimer’s disease-like pathology and cognitive decline. Nature Medicine [Epub ahead of print, November 25, 2012; doi: 10.1038/nm.2965].