title: Central Nervous System and Peripheral Inflammatory Processes in Alzheimer's Disease: Biomarker Profiling Approach.
abstract: Brain inflammation is one of the hallmarks of Alzheimer disease (AD) and a current trend is that inflammatory mediators, particularly cytokines and chemokines, may represent valuable biomarkers for early screening and diagnosis of the disease. Various studies have reported differences in serum level of cytokines, chemokines, and growth factors in patients with mild cognitive impairment or AD. However, data were often inconsistent and the exact function of inflammation in neurodegeneration is still a matter of debate. In the present work, we measured the expression of 120 biomarkers (corresponding to cytokines, chemokines, growth factors, and related signaling proteins) in the serum of 49 patients with the following diagnosis distribution: 15 controls, 14 AD, and 20 MCI. In addition, we performed the same analysis in the cerebrospinal fluid (CSF) of 20 of these patients (10 AD and 10 controls). Among the biomarkers tested, none showed significant changes in the serum, but 13 were significantly modified in the CSF of AD patients. Interestingly, all of these biomarkers were implicated in neurogenesis or neural stem cells migration and differentiation. In the second part of the study, 10 of these putative biomarkers (plus 4 additional) were quantified using quantitative multiplex ELISA methods in the CSF and the serum of an enlarged cohort composed of 31 AD and 24 control patients. Our results confirm the potential diagnosis interest of previously published blood biomarkers, and proposes new ones (such as IL-8 and TNFR-I). Further studies will be needed to validate these biomarkers which could be used alone, combined, or in association with the classical amyloid and tau biomarkers.
authors.affiliation: Laboratoire de Biochimie-Protéomique Clinique, Institute for Regenerative Medicine and Biotherapy (IRMB), CHU de Montpellier and Université Montpellier , Montpellier , France.
authors.forename: Constance
authors.initials: C
authors.lastname: Delaby
authors.affiliation: Laboratoire de Biochimie-Protéomique Clinique, Institute for Regenerative Medicine and Biotherapy (IRMB), CHU de Montpellier and Université Montpellier , Montpellier , France ; Centre Mémoire Ressource Recherche Languedoc Roussillon, Hôpital Gui de Chauliac, CHU de Montpellier , Montpellier , France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Gabelle
authors.affiliation: INSERM U837, CHU de Lille , Lille , France.
authors.forename: David
authors.initials: D
authors.lastname: Blum
authors.affiliation: INSERM U837, CHU de Lille , Lille , France.
authors.forename: Susanna
authors.initials: S
authors.lastname: Schraen-Maschke
authors.affiliation: Laboratoire de Biochimie-Protéomique Clinique, Institute for Regenerative Medicine and Biotherapy (IRMB), CHU de Montpellier and Université Montpellier , Montpellier , France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Moulinier
authors.affiliation: Laboratoire de Biochimie-Protéomique Clinique, Institute for Regenerative Medicine and Biotherapy (IRMB), CHU de Montpellier and Université Montpellier , Montpellier , France.
authors.forename: Justine
authors.initials: J
authors.lastname: Boulanghien
authors.affiliation: MGX-Montpellier GenomiX, Institut de Génomique Fonctionnelle , Montpellier , France.
authors.forename: Dany
authors.initials: D
authors.lastname: Séverac
authors.affiliation: INSERM U837, CHU de Lille , Lille , France.
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.affiliation: INSERM U1040, CHU de Montpellier , Montpellier , France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Rème
authors.affiliation: Laboratoire de Biochimie-Protéomique Clinique, Institute for Regenerative Medicine and Biotherapy (IRMB), CHU de Montpellier and Université Montpellier , Montpellier , France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehmann
keywords: Alzheimer disease; biomarkers; cerebrospinal fluid; inflammation; serum