title: Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease.
abstract: BACKGROUND
  Immunoreactivity for several chemokines and for their related receptors has been demonstrated in resident cells of the central nervous system, and the up-regulation of some of them is associated with pathological changes found in Alzheimer disease (AD).
  
  
  OBJECTIVE
  To determine interferon-gamma-inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP-1), and interleukin 8 (IL-8) levels in cerebrospinal fluid (CSF) from subjects with amnestic mild cognitive impairment (MCI) and patients with AD as compared with age-matched controls.
  
  
  METHODS
  Thirty-eight subjects with amnestic MCI, 36 patients with AD, and 41 age-matched subjects with noninflammatory affections of the nervous system.
  
  
  METHODS
  Evaluation of CSF chemokine production at time of diagnosis of MCI and AD; correlation with clinical and personal data. Longitudinal evaluation of subjects with MCI until conversion to AD.
  
  
  RESULTS
  Cerebrospinal fluid IP-10 concentration was significantly increased in patients with MCI and mild AD but not in patients with severe AD (Mini-Mental State Examination score <15), whereas MCP-1 and IL-8 levels were increased in patients with MCI and all patients with AD. A significant positive correlation between Mini-Mental State Examination score and CSF IP-10 or MCP-1 concentration was observed in patients with AD. No correlation between IP-10 levels and age was found, whereas MCP-1 and IL-8 levels correlated positively with age. Out of 38 subjects with MCI, 19 developed AD within a 1- to 3-year follow-up.
  
  
  CONCLUSIONS
  The presence of inflammatory molecules is likely to be a very early event in AD pathogenesis, even preceding the clinical onset of the disease, as demonstrated by subjects with MCI who developed AD over time. Interferon-gamma-inducible protein 10 is specifically increased in MCI and seems to decrease with the progression of AD, whereas MCP-1 and IL-8 are up-regulated also in late stages of the disease, suggesting a role in phases in which neurodegeneration is prevalent.
authors.affiliation: Department of Neurological Sciences, Dino Ferrari Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy. daniela.galimberti@unimi.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Niki
authors.initials: N
authors.lastname: Schoonenboom
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Femke
authors.initials: F
authors.lastname: Bouwman
authors.forename: Eliana
authors.initials: E
authors.lastname: Venturelli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Guidi
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Blankenstein
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D018932:Chemokine CCL2 / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D054357:Chemokine CXCL10; D018925:Chemokines / Q000134:cerebrospinal fluid* / Q000276:immunology*; D019743:Chemokines, CXC / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000276:immunology*; D004660:Encephalitis / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000276:immunology; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D013223:Statistics as Topic; D015854:Up-Regulation / Q000276:immunology
chemical_list: C111835:CCL2 protein, human; C114753:CXCL10 protein, human; D002556:Cerebrospinal Fluid Proteins; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D016209:Interleukin-8