| Summary |
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a marked decline in cognition and memory formation. Increasing evidence highlights the essential role of neuroinflammatory and immune-related molecules, namely the ones that are produced at the brain barriers, on brain immune surveillance, cellular dysfunction and amyloid beta (Aβ) pathology in AD. Therefore, understanding the response at the brain barriers may unravel novel pathways that are relevant 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 Aβ accumulation, and littermate age-matched wild-type (WT) mice, to characterize the CP transcriptome at 3, 5-6 and 11-12 months 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 3 months, which became lower than WT at 5-6 and 11-12 months. 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 3 months. Altogether, these findings provide new insights on a possible interplay between type I and type II IFN responses in AD and point to IFNs as mediators of cognitive decline in aging and in AD. |
