title: MicroRNA deregulation and chemotaxis and phagocytosis impairment in Alzheimer's disease.
abstract: BACKGROUND
  Mononuclear phagocytes play a critical role during Alzheimer's disease (AD) pathogenesis due to their contribution to innate immune responses and amyloid beta (Aβ) clearance mechanisms.
  
  
  METHODS
  Blood-derived monocytes (BDMs) and monocyte-derived macrophages (MDMs) were isolated from blood of AD, mild cognitive impairment (MCI) patients, and age-matched healthy controls for molecular and phenotypic comparisons.
  
  
  RESULTS
  The chemokine/chemokine receptor CCL2/CCR2 axis was impaired in BDMs from AD and MCI patients, causing a deficit in cell migration. Changes were also observed in MDM-mediated phagocytosis of Aβ fibrils, correlating with alterations in the expression and processing of the triggering receptor expressed on myeloid cells 2 (TREM2). Finally, immune-related microRNAs (miRNAs), including miR-155, -154, -200b, -27b, and -128, were found to be differentially expressed in these cells.
  
  
  CONCLUSIONS
  This work provides evidence that chemotaxis and phagocytosis, two crucial innate immune functions, are impaired in AD and MCI patients. Correlations with miRNA levels suggest an epigenetic contribution to systemic immune dysfunction in AD.
authors.affiliation: Doctoral Programme in Experimental Biology and Biomedicine, CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Joana R
authors.initials: JR
authors.lastname: Guedes
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Memory Clinic, Neurology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Santana
authors.affiliation: Memory Clinic, Neurology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Cunha
authors.affiliation: Memory Clinic, Neurology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Duro
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Almeida
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Cardoso
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal.
authors.forename: Maria C Pedroso
authors.initials: MC
authors.lastname: de Lima
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Cardoso
keywords: Alzheimer's disease; CCR2; Chemotaxis; Macrophages; Monocytes; Phagocytosis; TREM2; miRNAs