The DOI matches its Crossref record; 41 of the 42 references it cites were found in a registry or an index.
Intracerebral Production of Tumor Necrosis Factor-α, a Local Neuroprotective Agent, in Alzheimer Disease and Vascular Dementia
Abstract
The local pattern of proinflammatory cytokine release was studied in Alzheimer disease (AD) and vascular dementia (VAD), by measuring intrathecal levels of IL-1 beta, IL-6, TNF-alpha, and its naturally occurring antagonists, soluble TNF receptors I and II. The cytokine levels were related to neuronal damage, as measured by the intrathecal tau concentration, to cerebral apoptosis assessed by levels of Fas/APO-1 and bcl-2, and to clinical variables. In vitro analysis was performed to study the effect of TNF-alpha on the production of bcl-2, an antiapoptotic factor, by human neuronal cells. Patients with both AD and VAD displayed significantly higher intrathecal levels of TNF-alpha compared to controls. In addition, patients with AD showed significantly negative correlations between the intrathecal levels of TNF-alpha and the levels of Fas/APO-1 as well as of tau protein. The level of bcl-2 in supernatants of TNF-alpha-exposed cultures of human neuronal cells was up to three times higher than in control supernatants. Our study demonstrates intrathecal production of TNF-alpha in patients with dementias, suggesting that this cytokine may have a neuroprotective role in these neurodegenerative conditions as evidenced by negative correlations between this cytokine and (i) levels of intrathecal Fas/APO-1 and (ii) levels of tau protein, both parameters closely related to brain damage. Our in vitro data suggest that TNF-alpha exerts its neuroprotective effect by stimulating neuronal cells to express bcl-2, a molecule which downregulates apoptosis.
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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 [145]
Citations
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Inflammation and Alzheimer’s disease
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Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease.
(2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2305-5839.2015.03.49 · Cited by 1,288
A Meta-Analysis of Cytokines in Alzheimer's Disease
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Self-citationClassification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins
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Self-citation
Metadata
- Authors
- Tarkowski, E., Blennow, K., Wallin, A., & Tarkowski, A.
- Affiliations
- University of Gothenburg (SE)
- Varberg Hospital (SE)
- ORCID
- Blennow, Kaj
- Venue
- Journal of Clinical Immunology
- Published
- 1999-07
- Volume
- 19
- Issue
- 4
- Pages
- 223-230
- ISSN
- 0271-9142 (ISSN-L)
- 1573-2592
- OpenAlex
- W231832547
- Cited by
- 349
- References
- 42
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 18 · 2023: 11 · 2022: 2 · 2021: 8 · 2020: 15 · 2019: 5 · 2018: 7 · 2017: 12 · 2016: 12 · 2015: 13 · 2014: 24 · 2013: 7 · 2012: 18
- FWCI
- 8.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- TNF-α, Alzheimer's disease, vascular dementia, neuroinflammation, neuroprotection, apoptosis, Fas/APO-1, Bcl-2, tau protein, soluble TNF receptors, inflammatory cytokines, neuronal injury
- MeSH terms
- Aged, Alzheimer Disease, Brain, Female, Humans, Interleukin-1, Male, Middle Aged, Neurons, Tumor Necrosis Factor-alpha, Dementia, Vascular, Interleukin-6, tau Proteins, Apoptosis, Receptors, Tumor Necrosis Factor, Neuroprotective Agents, fas Receptor, Proto-Oncogene Proteins c-bcl-2
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