The choroid plexus transcriptome reveals changes in type I and II interferon responses in a mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a marked decline in cognition and memory function. Increasing evidence highlights the essential role of neuroinflammatory and immune-related molecules, including those produced at the brain barriers, on brain immune surveillance, cellular dysfunction and amyloid beta (Aß) pathology in AD. Therefore, understanding the response at the brain barriers may unravel novel pathways of relevance for the pathophysiology of AD. Herein, we focused on the study of the choroid plexus (CP), which constitutes the blood-cerebrospinal fluid barrier, in aging and in AD. Specifically, we used the PDGFB-APPSwInd (J20) transgenic mouse model of AD, which presents early memory decline and progressive Aß accumulation, and littermate age-matched wild-type (WT) mice, to characterize the CP transcriptome at 3, 5-6 and 11-12months of age. The most striking observation was that the CP of J20 mice displayed an overall overexpression of type I interferon (IFN) response genes at all ages. Moreover, J20 mice presented a high expression of type II IFN genes in the CP at 3months, which became lower than WT at 5-6 and 11-12months. Importantly, along with a marked memory impairment and increased glial activation, J20 mice also presented a similar overexpression of type I IFN genes in the dorsal hippocampus at 3months. Altogether, these findings provide new insights on a possible interplay between type I and II IFN responses in AD and point to IFNs as targets for modulation in cognitive decline.The authors would like to acknowledge Pedro Moreira, Madalena Esteves and Dr. Patricio Costa (all from the ICVS/3B's - PT Government Associate Laboratory) for comments and scientific input regarding the statistical analysis of this study. Sandro Da Mesquita and Ana C. Ferreira are recipients of PhD fellowships by the Fundacao para a Ciencia e Tecnologia (FCT, Portugal)/FEDER and Programa Operacional Potencial Humano (POPH/FSE), references SFRH/BD/69706/2010 and SFRH/BD/51989/2012, respectively. Fernanda Marques is an assistant researcher and recipient of a FCT Investigator Grant with the reference IF/00231/2013. This work was supported by FCT and COMPETE through the project EXPL/NEU-OSD/2196/2013 and the Bial Foundation through the Grant 217/12