title: Peripheral blood mono-nuclear cells derived from Alzheimer's disease patients show elevated baseline levels of secreted cytokines but resist stimulation with β-amyloid peptide.
abstract: OBJECTIVE
  Among several other factors, the neuro-toxic β-amyloid peptide (βAP)-induced inflammatory mechanisms have also been implicated in the pathogenesis of Alzheimer's dementia (AD). Cytokines have recently emerged as prime candidates underlying this immune reaction. The purpose of this study was to evaluate the inflammatory response of peripheral blood mono-nuclear cells (PBMC) in AD.
  
  
  METHODS
  Cross-sectional (observational) study.
  
  
  METHODS
  Behavioral and cognitive neurology clinic of the Universidade Federal de Minas Gerais in Belo Horizonte, Brazil.
  
  
  METHODS
  AD patients (n=19), healthy elderly (n=19) and young (n=14) individuals.
  
  
  METHODS
  Cytokine levels were assessed by enzyme-linked immuno-sorbent assay (ELISA) after exposing cells to a broad range of βAP concentrations (10(-4)-10(-10)M) as a stimulus. AD samples were weighed against leukocytes harvested from non-demented young and elderly subjects.
  
  
  RESULTS
  Cytokine production of PBMCs in the youth was characterized by low baseline levels when compared to cells from the older generation. In the aging population, AD cells were distinguished from the healthy elderly sub-group by an even higher basal cytokine secretion. The low resting concentration in young individuals was markedly increased after treatment with βAP, however cells from the elderly, irrespective of their disease status, showed unchanged cytokine release following βAP administration. Non-specific activation of PBMCs with anti-CD3/CD28 antibodies resulted in elevated interleukin (IL)-1β concentrations in AD.
  
  
  CONCLUSIONS
  These results demonstrate a general over-production of cytokines and resistance to βAP in the old comparison group, with a more pronounced disruption/boosted pattern in AD. Our findings are in line with the hypothesis of "inflammaging", i.e. an enhanced inflammatory profile with normal aging and a further perturbed environment in AD. The observed cytokine profiles may serve as diagnostic biomarkers in dementia.
authors.affiliation: Laboratório de Neurofarmacologia, Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (ICB-UFMG), Avenida Antônio Carlos 6627, 31270-901 Campus Pampulha, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Natália Pessoa
authors.initials: NP
authors.lastname: Rocha
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Alfredo Balena 190, 30130-100 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Antônio Lúcio
authors.initials: AL
authors.lastname: Teixeira
authors.affiliation: Laboratório de Neurofarmacologia, Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (ICB-UFMG), Avenida Antônio Carlos 6627, 31270-901 Campus Pampulha, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Fernanda Matos
authors.initials: FM
authors.lastname: Coelho
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Alfredo Balena 190, 30130-100 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Paulo
authors.initials: P
authors.lastname: Caramelli
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Alfredo Balena 190, 30130-100 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Henrique Cerqueira
authors.initials: HC
authors.lastname: Guimarães
authors.affiliation: Laboratório de Neurofarmacologia, Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (ICB-UFMG), Avenida Antônio Carlos 6627, 31270-901 Campus Pampulha, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Izabela Guimarães
authors.initials: IG
authors.lastname: Barbosa
authors.affiliation: Laboratório de Neurofarmacologia, Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (ICB-UFMG), Avenida Antônio Carlos 6627, 31270-901 Campus Pampulha, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Tarcilia Aparecida
authors.initials: TA
authors.lastname: da Silva
authors.affiliation: Department of Physiology, Kazan State Medical University, ul. Butlerova 49, R-420012 Kazan, Russia.
authors.forename: Marat Alexandrovich
authors.initials: MA
authors.lastname: Mukhamedyarov
authors.affiliation: Department of Physiology, Kazan State Medical University, ul. Butlerova 49, R-420012 Kazan, Russia.
authors.forename: Andrey Lvovich
authors.initials: AL
authors.lastname: Zefirov
authors.affiliation: Department of Genetics, Faculty of Biology and Soil Sciences, Kazan Federal University, ul. Kremlevskaya 18, R-420008 Kazan, Russia; Core Research Laboratory, Kazan State Medical University, ul. Butlerova 49, R-420012 Kazan, Russia; Department of Genetics and Bioengineering, College of Engineering and Architecture, Yeditepe University, 26 Ağustos Campus, Kayisdagi cad., Kayisdagi, 34755 Istanbul, Turkey; Republic Clinical Hospital, ul. Orenburg tract 138, R-420064 Kazan, Russia.
authors.forename: Albert Anatolyevich
authors.initials: AA
authors.lastname: Rizvanov
authors.affiliation: Republic Clinical Hospital, ul. Orenburg tract 138, R-420064 Kazan, Russia; Department of Anatomy, Kazan State Medical University, ul. Butlerova 49, R-420012 Kazan, Russia.
authors.forename: Andrey Pavlovich
authors.initials: AP
authors.lastname: Kiyasov
authors.affiliation: Laboratório de Neurofarmacologia, Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (ICB-UFMG), Avenida Antônio Carlos 6627, 31270-901 Campus Pampulha, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Luciene B
authors.initials: LB
authors.lastname: Vieira
authors.affiliation: Department of Psychiatry, Albert Szent-Györgyi Clinical Center, Faculty of Medicine, University of Szeged, H-6721 Szeged, Semmelweis u. 6, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Janka
authors.affiliation: Asklepios-Med (private medical practice and research center), H-6722 Szeged, Kossuth Lajos sgt. 23, Hungary. Electronic address: palotas@asklepios-med.eu.
authors.forename: András
authors.initials: A
authors.lastname: Palotás
authors.affiliation: Laboratório de Neurofarmacologia, Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (ICB-UFMG), Avenida Antônio Carlos 6627, 31270-901 Campus Pampulha, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Helton José
authors.initials: HJ
authors.lastname: Reis
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines