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Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease.
Arch Neurol 2006; 63(4):538-43AN

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.

Authors+Show Affiliations

Department of Neurological Sciences, Dino Ferrari Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy. daniela.galimberti@unimi.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16606766

Citation

Galimberti, Daniela, et al. "Intrathecal Chemokine Synthesis in Mild Cognitive Impairment and Alzheimer Disease." Archives of Neurology, vol. 63, no. 4, 2006, pp. 538-43.
Galimberti D, Schoonenboom N, Scheltens P, et al. Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease. Arch Neurol. 2006;63(4):538-43.
Galimberti, D., Schoonenboom, N., Scheltens, P., Fenoglio, C., Bouwman, F., Venturelli, E., ... Scarpini, E. (2006). Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease. Archives of Neurology, 63(4), pp. 538-43.
Galimberti D, et al. Intrathecal Chemokine Synthesis in Mild Cognitive Impairment and Alzheimer Disease. Arch Neurol. 2006;63(4):538-43. PubMed PMID: 16606766.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease. AU - Galimberti,Daniela, AU - Schoonenboom,Niki, AU - Scheltens,Philip, AU - Fenoglio,Chiara, AU - Bouwman,Femke, AU - Venturelli,Eliana, AU - Guidi,Ilaria, AU - Blankenstein,Marinus A, AU - Bresolin,Nereo, AU - Scarpini,Elio, PY - 2006/4/12/pubmed PY - 2006/5/23/medline PY - 2006/4/12/entrez SP - 538 EP - 43 JF - Archives of neurology JO - Arch. Neurol. VL - 63 IS - 4 N2 - 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. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/16606766/Intrathecal_chemokine_synthesis_in_mild_cognitive_impairment_and_Alzheimer_disease_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneur.63.4.538 DB - PRIME DP - Unbound Medicine ER -