Intrathecal Chemokine Synthesis in Mild Cognitive Impairment and Alzheimer Disease
Open accessAbstract
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.
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- Authors
- Galimberti, D., Schoonenboom, N., Scheltens, P., Fenoglio, C., Bouwman, F., Venturelli, E., Guidi, I., Blankenstein, M. A., Bresolin, N., & Scarpini, E.
- Affiliations
- University of Milan (IT)
- Vrije Universiteit Amsterdam (NL)
- Neurology, Inc (US)
- ORCID
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2006-04-01
- Volume
- 63
- Issue
- 4
- Pages
- 538
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2158143414
- Cited by
- 289
- References
- 37
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 13 · 2023: 16 · 2022: 11 · 2021: 24 · 2020: 15 · 2019: 17 · 2018: 11 · 2017: 14 · 2016: 11 · 2015: 13 · 2014: 20 · 2013: 13 · 2012: 15
- FWCI
- 10.76
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- other-oa
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, mild cognitive impairment, chemokines, cerebrospinal fluid, CXCL10, MCP-1, interleukin-8, neuroinflammation, disease progression, neurodegeneration, cognitive decline
- MeSH terms
- Aged, Alzheimer Disease, Brain, Cerebrospinal Fluid Proteins, Cognition Disorders, Encephalitis, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Predictive Value of Tests, Statistics as Topic, Up-Regulation, Interleukin-8, Chemokines, Chemokine CCL2, Chemokines, CXC, Chemokine CXCL10
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