Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease

Arch Neurol. 2006 Apr;63(4):538-43. doi: 10.1001/archneur.63.4.538.


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.

Patients: Thirty-eight subjects with amnestic MCI, 36 patients with AD, and 41 age-matched subjects with noninflammatory affections of the nervous system.

Design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / immunology*
  • Brain / immunology
  • Brain / metabolism
  • Brain / physiopathology
  • Cerebrospinal Fluid Proteins / analysis
  • Cerebrospinal Fluid Proteins / immunology
  • Cerebrospinal Fluid Proteins / metabolism
  • Chemokine CCL2 / analysis
  • Chemokine CCL2 / immunology
  • Chemokine CCL2 / metabolism
  • Chemokine CXCL10
  • Chemokines / cerebrospinal fluid*
  • Chemokines / immunology*
  • Chemokines, CXC / analysis
  • Chemokines, CXC / immunology
  • Chemokines, CXC / metabolism
  • Cognition Disorders / cerebrospinal fluid*
  • Cognition Disorders / diagnosis
  • Cognition Disorders / immunology*
  • Encephalitis / cerebrospinal fluid
  • Encephalitis / diagnosis
  • Encephalitis / immunology
  • Female
  • Humans
  • Interleukin-8 / analysis
  • Interleukin-8 / immunology
  • Interleukin-8 / metabolism
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Predictive Value of Tests
  • Statistics as Topic
  • Up-Regulation / immunology


  • CCL2 protein, human
  • CXCL10 protein, human
  • Cerebrospinal Fluid Proteins
  • Chemokine CCL2
  • Chemokine CXCL10
  • Chemokines
  • Chemokines, CXC
  • Interleukin-8