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Intrathecal Chemokine Synthesis in Mild Cognitive Impairment and Alzheimer Disease
Daniela Galimberti, PhD;
Niki Schoonenboom, MD;
Philip Scheltens, MD, PhD;
Chiara Fenoglio, PhD;
Femke Bouwman, MD;
Eliana Venturelli, PhD;
Ilaria Guidi, MD;
Marinus A. Blankenstein, PhD;
Nereo Bresolin, MD;
Elio Scarpini, MD
Arch Neurol. 2006;63:538-543.
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- -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--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.
Author Affiliations: Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Milan, Italy (Drs Galimberti, Fenoglio, Venturelli, Guidi, Bresolin, and Scarpini); Department of Neurology and Alzheimer Center (Drs Schoonenboom, Scheltens, and Bouwman) and Department of Clinical Chemistry (Drs Schoonenboom and Blankenstein), VU Medical Center, Amsterdam, the Netherlands.
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