title: Leukocyte Telomere Length in Alzheimer's Disease Patients with a Different Rate of Progression.
abstract: BACKGROUND
  Age and short leukocyte telomeres have been associated with a higher risk of Alzheimer's disease (AD). Inflammation is involved in AD and it is suggested that anti-inflammatory interleukin-10 (IL-10) may partly antagonize these processes.
  
  
  OBJECTIVE
  The aim is to correlate telomere length (TL) in peripheral blood mononuclear cells (PBMC) from patients with AD to disease progression rate. Moreover, we evaluated whether TL was associated with IL-10 production by unstimulated or amyloid-β (Aβ)-stimulated PBMC.
  
  
  METHODS
  We enrolled 31 late-onset AD and 20 age-matched healthy elderly (HE). After a two-year follow-up period, patients were retrospectively evaluated as slow-progressing (ADS) (Mini Mental State Examination (MMSE) decline over the two years of follow-up ≤3 points) or fast progressing AD (ADF) (MMSE decline ≥5 points). TL was measured by flow cytometry and in vitro IL-10 production by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  TL (mean±SD) for HE, ADS, and ADF was 2.3±0.1, 2.0±0.1, and 2.5±0.1 Kb, respectively. ADS showed a shorter TL compared to HE (p = 0.034) and to ADF (p = 0.005). MMSE decline correlated with TL in AD (R2 = 0.284; p = 0.008). We found a significant difference in IL-10 production between unstimulated and Aβ-stimulated PBMC from ADS (40.7±13.7 versus 59.0±27.0; p = 0.004) but not from ADF (39.7±14.4 versus 42.2±22.4). HE showed a trend toward significance (47.1±25.4 versus 55.3±27.9; p = 0.10).
  
  
  CONCLUSIONS
  PBMC from ADF may be characterized by an impaired response induced by Aβ and by a reduced proliferative response responsible for the longer telomeres. TL might be a contributing factor in predicting the rate of AD progression.
authors.affiliation: Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Tedone
authors.affiliation: Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Milan, Italy.|Geriatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Arosio
authors.affiliation: Flow Cytometry Service, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Colombo
authors.affiliation: Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ferri
authors.affiliation: ImmunoClin Ltd, London, UK.|UPMC University Paris 06, UMR 8526 Biological Adaptation and Ageing (B2A) Team Brain Development, Repair and Aging (BDRA), Paris, France.|CNRS, UMR 8526 Biological Adaptation and Ageing (B2A) Team Brain Development, Repair and Aging (BDRA), Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Asselineau
authors.affiliation: AP-HP, DHU FAST GH Pitie-Salpêtrière-Charles Foix, Paris, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Piette
authors.affiliation: Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gussago
authors.affiliation: AP-HP, DHU FAST GH Pitie-Salpêtrière-Charles Foix, Paris, France.
authors.forename: Joel
authors.initials: J
authors.lastname: Belmin
authors.affiliation: AP-HP, DHU FAST GH Pitie-Salpêtrière-Charles Foix, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Pariel
authors.affiliation: ImmunoClin Ltd, London, UK.
authors.forename: Khadija
authors.initials: K
authors.lastname: Benlhassan
authors.affiliation: Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Casati
authors.affiliation: AP-HP, DHU FAST GH Pitie-Salpêtrière-Charles Foix, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Bornand
authors.affiliation: Geriatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Paolo Dionigi
authors.initials: PD
authors.lastname: Rossi
authors.affiliation: Geriatric Clinic, Department of Health Science, Milan Center for Neuroscience, University Study of Milano-Bicocca, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Mazzola
authors.affiliation: Geriatric Clinic, Department of Health Science, Milan Center for Neuroscience, University Study of Milano-Bicocca, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Annoni
authors.affiliation: UPMC University Paris 06, UMR 8526 Biological Adaptation and Ageing (B2A) Team Brain Development, Repair and Aging (BDRA), Paris, France.|CNRS, UMR 8526 Biological Adaptation and Ageing (B2A) Team Brain Development, Repair and Aging (BDRA), Paris, France.|AP-HP, DHU FAST GH Pitie-Salpêtrière-Charles Foix, Paris, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Doulazmi
authors.affiliation: UPMC University Paris 06, UMR 8526 Biological Adaptation and Ageing (B2A) Team Brain Development, Repair and Aging (BDRA), Paris, France.|CNRS, UMR 8526 Biological Adaptation and Ageing (B2A) Team Brain Development, Repair and Aging (BDRA), Paris, France.|AP-HP, DHU FAST GH Pitie-Salpêtrière-Charles Foix, Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Mariani
authors.affiliation: Flow Cytometry Service, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Porretti
authors.affiliation: ImmunoClin Ltd, London, UK.
authors.forename: Dorothy H
authors.initials: DH
authors.lastname: Bray
authors.affiliation: Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Milan, Italy.|Geriatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mari
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008609:Mental Status Schedule; D012333:RNA, Messenger / Q000378:metabolism; D016615:Telomere / Q000235:genetics* / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10
keywords: Alzheimer’s disease; disease progression; interleukin-10; peripheral blood mononuclear cells; telomere