title: Inflammatory Stress on Autophagy in Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease during 24 Months of Follow-Up.
abstract: Recent findings indicate that microglia in Alzheimer's disease (AD) is senescent whereas peripheral blood mononuclear cells (PBMCs) could infiltrate the brain to phagocyte amyloid deposits. However, the molecular mechanisms involved in the amyloid peptide clearance remain unknown. Autophagy is a physiological degradation of proteins and organelles and can be controlled by pro-inflammatory cytokines. The purpose of this study was to evaluate the impact of inflammation on autophagy in PBMCs from AD patients at baseline, 12 and 24 months of follow-up. Furthermore, PBMCs from healthy patients were also included and treated with 20 μM amyloid peptide 1-42 to mimic AD environment. For each patient, PBMCs were stimulated with the mitogenic factor, phytohaemagglutin (PHA), and treated with either 1 μM C16 as an anti-inflammatory drug or its vehicle. Autophagic markers (Beclin-1, p62/sequestosome 1 and microtubule-associated protein-light chain 3: LC3) were quantified by western blot and cytokines (Interleukin (IL)-1β, Tumor necrosis Factor (TNF)-α and IL-6) by Luminex X-MAP® technology. Beclin-1 and TNF-α levels were inversely correlated in AD PBMCs at 12 months post-inclusion. In addition, Beclin-1 and p62 increased in the low inflammatory environment induced by C16. Only LC3-I levels were inversely correlated with cognitive decline at baseline. For the first time, this study describes longitudinal changes in autophagic markers in PBMCs of AD patients under an inflammatory environment. Inflammation would induce autophagy in the PBMCs of AD patients while an anti-inflammatory environment could inhibit their autophagic response. However, this positive response could be altered in a highly aggressive environment.
authors.affiliation: EA3808 Molecular Targets and Therapeutics of Alzheimer's Disease, University of Poitiers, Poitiers, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: François
authors.affiliation: EA3808 Molecular Targets and Therapeutics of Alzheimer's Disease, University of Poitiers, Poitiers, France; Neurology Department, Poitiers University Hospital, Poitiers, France; Centre Mémoire de Ressources et de Recherche, Poitiers University Hospital, Poitiers, France; Geriatrics Department, Poitiers University Hospital, Poitiers, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Julian
authors.affiliation: CIC-P 1402, Poitiers University Hospital, Poitiers, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Ragot
authors.affiliation: EA3808 Molecular Targets and Therapeutics of Alzheimer's Disease, University of Poitiers, Poitiers, France; CIC-P 1402, Poitiers University Hospital, Poitiers, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Dugast
authors.affiliation: Geriatrics Department, Poitiers University Hospital, Poitiers, France; CIC-P 1402, Poitiers University Hospital, Poitiers, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Blanchard
authors.affiliation: CIC-P 1402, Poitiers University Hospital, Poitiers, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Brishoual
authors.affiliation: EA3808 Molecular Targets and Therapeutics of Alzheimer’s disease, University of Poitiers, Poitiers, France; University of Limoges, Laboratory of Histology and Biology, Faculty of Medicine, Limoges; Service d’histologie et de cytogénétique, Hôpital de la Mère et de l’Enfant, Limoges, France.
authors.forename: Faraj
authors.initials: F
authors.lastname: Terro
authors.affiliation: EA3808 Molecular Targets and Therapeutics of Alzheimer's Disease, University of Poitiers, Poitiers, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Chassaing
authors.affiliation: EA3808 Molecular Targets and Therapeutics of Alzheimer's Disease, University of Poitiers, Poitiers, France.
authors.forename: Guylène
authors.initials: G
authors.lastname: Page
authors.affiliation: EA3808 Molecular Targets and Therapeutics of Alzheimer's Disease, University of Poitiers, Poitiers, France; Centre Mémoire de Ressources et de Recherche, Poitiers University Hospital, Poitiers, France; Geriatrics Department, Poitiers University Hospital, Poitiers, France; CIC-P 1402, Poitiers University Hospital, Poitiers, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Paccalin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D001343:Autophagy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*