Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease.
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.
Galimberti
Daniela
D
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
Schoonenboom
Niki
N
Scheltens
Philip
P
Fenoglio
Chiara
C
Bouwman
Femke
F
Venturelli
Eliana
E
Guidi
Ilaria
I
Blankenstein
Marinus A
MA
Bresolin
Nereo
N
Scarpini
Elio
E
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
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