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

Sandro Dá Mesquita, Ana C. Ferreira, Fuying Gao, Giovanni Coppola, Daniel H. Geschwind, João C. Sousa, Margarida Correia-Neves, Nuno Sousa, Joana A. Palha, Fernanda Marques

Research output: Contribution to journalArticlepeer-review


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 (Aβ) 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 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 II IFN responses in AD and point to IFNs as targets for modulation in cognitive decline.

Original languageEnglish (US)
Pages (from-to)280-292
Number of pages13
JournalBrain, Behavior, and Immunity
StatePublished - Oct 1 2015


  • Aging
  • Alzheimer's disease
  • Cerebrospinal fluid
  • Choroid plexus
  • Glial cells
  • Hippocampus
  • Interferons
  • Memory
  • Neuroinflammation
  • Transcriptome

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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