title: The choroid plexus transcriptome reveals changes in type I and II interferon responses in a mouse model of Alzheimer's disease.
abstract: 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 11-12months 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.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimaraes, Portugal.
authors.forename: Sandro Dá
authors.initials: SD
authors.lastname: Mesquita
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimaraes, Portugal.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Ferreira
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine - University of California, Los Angeles, CA, USA.
authors.forename: Fuying
authors.initials: F
authors.lastname: Gao
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine - University of California, Los Angeles, CA, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine - University of California, Los Angeles, CA, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimaraes, Portugal.
authors.forename: João C
authors.initials: JC
authors.lastname: Sousa
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimaraes, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Correia-Neves
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimaraes, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Sousa
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimaraes, Portugal.
authors.forename: Joana A
authors.initials: JA
authors.lastname: Palha
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimaraes, Portugal. Electronic address: fmarques@ecsaude.uminho.pt.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Marques
mesh_terms: D000375:Aging / Q000235:genetics / Q000523:psychology; D000544:Alzheimer Disease / Q000235:genetics* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002831:Choroid Plexus / Q000378:metabolism*; D004195:Disease Models, Animal; D007370:Interferon Type I / Q000134:cerebrospinal fluid / Q000235:genetics*; D007371:Interferon-gamma / Q000134:cerebrospinal fluid / Q000235:genetics*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D059467:Transcriptome
chemical_list: D016229:Amyloid beta-Peptides; D007370:Interferon Type I; D007371:Interferon-gamma
keywords: Aging; Alzheimer’s disease; Cerebrospinal fluid; Choroid plexus; Glial cells; Hippocampus; Interferons; Memory; Neuroinflammation; Transcriptome