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Arch Neurol. 2006 Apr;63(4):538-43.

Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease.

Author information

1
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

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.

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.

PMID:
16606766
DOI:
10.1001/archneur.63.4.538
[Indexed for MEDLINE]

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