Intracerebral Production of Tumor Necrosis Factor-α, a Local Neuroprotective Agent, in Alzheimer Disease and Vascular Dementia

Tarkowski, Elisabeth; Blennow, Kaj; Wallin, Anders; Tarkowski, Andrzej

doi:10.1023/a:1020568013953

Cited by 349Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

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Intracerebral Production of Tumor Necrosis Factor-α, a Local Neuroprotective Agent, in Alzheimer Disease and Vascular Dementia

Tarkowski, Elisabeth, Blennow, Kaj, Wallin, Anders, Tarkowski, Andrzej·1999·Journal of Clinical Immunology

DOI 10.1023/a:1020568013953

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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 are elevated in the CSF of AD patients and correlate with disease progression.
“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]

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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
Publisher: Springer Science and Business Media LLC
Published: 1999-07
Volume: 19
Issue: 4
Pages: 223-230
ISSN: 0271-9142 (ISSN-L)
1573-2592
DOI: 10.1023/a:1020568013953
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: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
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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Intracerebral Production of Tumor Necrosis Factor-α, a Local Neuroprotective Agent, in Alzheimer Disease and Vascular Dementia

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