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Intrathecal inflammation precedes development of Alzheimer's disease
Open accessAbstract
OBJECTIVES: To analyse the cerebrospinal fluid (CSF) values of the proinflammatory cytokines, interleukin 1beta (IL1beta), tumour necrosis factor alpha (TNFalpha), GM-CSF, of the anti-inflammatory cytokine TGFbeta, of tau protein, a marker for neurodegeneration, and of beta amyloid (Abeta), a protein involved in the formation of senile plaques, in prospectively followed up patients with mild cognitive impairment (MCI). METHODS: Analyses of CSF levels of TNFalpha, IL1beta, GM-CSF, TGFbeta, betaa, and tau protein were performed using ELISA in 56 patients with MCI who were followed up prospectively and in 25 age matched, healthy controls. RESULTS: Patients with MCI displayed significantly higher levels of TNFalpha and tau protein and significantly lower levels of TGFbeta and Abeta compared with the healthy controls. After nine months of follow up, 25 patients still displayed MCI while the remaining 31 patients had progressed to Alzheimer's disease (AD). Only MCI patients who progressed to AD at follow up, showed significantly higher CSF levels of TNFalpha than controls. In addition, reduced CSF-Abeta42 levels were only found in MCI patients that progressed to AD, further supporting the notion that disturbed metabolism of Abeta is an early finding in AD. CONCLUSIONS: These results demonstrate increased production of the proinflammatory cytokine, TNFalpha and decreased production of the anti-inflammatory cytokine TGFbeta in patients with MCI at risk to develop AD, suggesting a propensity towards inflammation in this patient group and indicating that CNS inflammation is a early hallmark in the pathogenesis of AD.
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“TNF-α levels were also found to be elevated in the CSF of AD patients and correlate with disease progression [145, 146].”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [146]
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Metadata
- Authors
- Tarkowski, E.
- Affiliations
- University of Gothenburg (SE)
- Corresponding author
- Tarkowski, E
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2003-09-01
- Volume
- 74
- Issue
- 9
- Pages
- 1200-1205
- ISSN
- 0022-3050 (ISSN-L)
- PMC
- PMC1738668
- OpenAlex
- W2071728536
- Cited by
- 501
- References
- 53
- Citations by year
- 2026: 16 · 2025: 17 · 2024: 45 · 2023: 28 · 2022: 43 · 2021: 51 · 2020: 23 · 2019: 30 · 2018: 32 · 2017: 23 · 2016: 18 · 2015: 16 · 2014: 14 · 2013: 13 · 2012: 18
- FWCI
- 6.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Rune och Ulla Amlövs Stiftelse för Neurologisk och Reumatologisk Forskning
- Hjärt-Lungfonden
- Göteborgs Läkaresällskap
- Svenska Läkaresällskapet
- Stiftelsen Konung Gustaf V:s 80-årsfond
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, mild cognitive impairment, cerebrospinal fluid biomarkers, intrathecal inflammation, inflammatory cytokines, TNF-α, IL-1β, GM-CSF, TGF-beta, tau protein, amyloid-beta, amyloid metabolism, neuroinflammation, disease progression
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Central Nervous System, Cognition Disorders, Female, Humans, Inflammation, Interleukin-1, Male, Middle Aged, Prospective Studies, Risk Factors, Tumor Necrosis Factor-alpha, Granulocyte-Macrophage Colony-Stimulating Factor, Amyloid beta-Peptides, tau Proteins, Plaque, Amyloid
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