title: Subtype and regional-specific neuroinflammation in sporadic creutzfeldt-jakob disease.
abstract: The present study identifies deregulated cytokines and mediators of the immune response in the frontal cortex and cerebellum of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 and VV2 subtypes compared to age-matched controls. Deregulated genes include pro- and anti-inflammatory cytokines, toll-like receptors, colony stimulating factors, cathepsins, members of the complement system, and members of the integrin and CTL/CTLD family with particular regional and sCJD subtype patterns. Analysis of cytokines and mediators at protein level shows expression of selected molecules and receptors in neurons, in astrocytes, and/or in microglia, thus suggesting interactions between neurons and glial cells, mainly microglia, in the neuroinflammatory response in sCJD. Similar inflammatory responses have been shown in the tg340 sCJD MM1 mice, revealing a progressive deregulation of inflammatory mediators with disease progression. Yet, inflammatory molecules involved are subjected to species differences in humans and mice. Moreover, inflammatory-related cell signaling pathways NFκB/IKK and JAK/STAT are activated in sCJD and sCJD MM1 mice. Together, the present observations show a self-sustained complex inflammatory and inflammatory-related responses occurring already at early clinical stages in animal model and dramatically progressing at advanced stages of sCJD. Considering this scenario, measures tailored to modulate (activate or inhibit) specific molecules could be therapeutic options in CJD.
authors.affiliation: Department of Neurology, Clinical Dementia Center and DZNE, University Medical School, Georg-August University , Göttingen , Germany ; Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, University of Barcelona, Hospitalet de Llobregat , Barcelona , Spain.
authors.forename: Franc
authors.initials: F
authors.lastname: Llorens
authors.affiliation: Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, University of Barcelona, Hospitalet de Llobregat , Barcelona , Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: López-González
authors.affiliation: Department of Neurology, Clinical Dementia Center and DZNE, University Medical School, Georg-August University , Göttingen , Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Thüne
authors.affiliation: Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, University of Barcelona, Hospitalet de Llobregat , Barcelona , Spain ; Network Center for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Institute Carlos III, Ministry of Health , Madrid , Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Carmona
authors.affiliation: Department of Neurology, Clinical Dementia Center and DZNE, University Medical School, Georg-August University , Göttingen , Germany.
authors.forename: Saima
authors.initials: S
authors.lastname: Zafar
authors.affiliation: Ecole Nationale Vétérinaire de Toulouse, Institut National de la Recherche Agronomique , Toulouse , France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Andréoletti
authors.affiliation: Department of Neurology, Clinical Dementia Center and DZNE, University Medical School, Georg-August University , Göttingen , Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
authors.affiliation: Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, University of Barcelona, Hospitalet de Llobregat , Barcelona , Spain ; Network Center for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Institute Carlos III, Ministry of Health , Madrid , Spain.
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
keywords: Creutzfeldt–Jakob disease; cytokines; microglia; neuroinflammation; prion protein