Activation of microglial cells by β-amyloid protein and interferon-γ

Meda, Lucia; Cassatella, Marco A.; Szendrei, Gyorgyi I.; Otvos, Laszlo; Baron, Pierluigi; Villalba, Martin; Ferrari, Davide; Rossi, Filippo

doi:10.1038/374647a0

Cited by 1,314Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Activation of microglial cells by β-amyloid protein and interferon-γ

Meda, Lucia, Cassatella, Marco A., Szendrei, Gyorgyi I., Otvos, Laszlo, Baron, Pierluigi, Villalba, Martin, Ferrari, Davide, Rossi, Filippo·1995·Nature

DOI 10.1038/374647a0

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Abstract

Alzheimer's disease is the most common cause of progressive intellectual failure. The lesions that develop, called senile plaques, are extracellular deposits principally composed of insoluble aggregates of beta-amyloid protein (A beta), infiltrated by reactive microglia and astrocytes. Although A beta, and a portion of it, the fragment 25-35 (A beta (25-35)), have been shown to exert a direct toxic effect on neurons, the role of microglia in such neuronal injury remains unclear. Here we report a synergistic effect between A beta and interferon-gamma (IFN-gamma) in triggering the production of reactive nitrogen intermediates and tumour-necrosis factor-alpha (TNF-alpha) from microglia. Furthermore, using co-culture experiments, we show that activation of microglia with IFN-gamma and A beta leads to neuronal cell injury in vitro. These findings suggest that A beta and IFN-gamma activate microglia to produce reactive nitrogen intermediates and TNF-alpha, and this may have a role in the pathogenesis of neuronal degeneration observed in ageing and Alzheimer's disease.

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Aβ can induce cytokine release from microglia, hence aggravating the pathology.
“Moreover, Aβ can induce cytokine release from microglia, hence aggravating the pathology (32).”
From Deletion of Abi3 gene locus exacerbates neuropathological features of Alzheimer’s disease in a mouse model of Aβ amyloidosis (2021) · cites this paper as [32]

A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease.
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Authors: Meda, L., Cassatella, M. A., Szendrei, G. I., Otvos, L., Baron, P., Villalba, M., Ferrari, D., & Rossi, F.
Affiliations: University of Verona (IT)
University of Milan (IT)
University of Ferrara (IT)
ORCID: Cassatella, Marco A.
Ferrari, Davide
Rossi, Filippo
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1995-04
Volume: 374
Issue: 6523
Pages: 647-650
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/374647a0
OpenAlex: W1991763618
Cited by: 1,314
References: 2
Citations by year: 2026: 7 · 2025: 18 · 2024: 15 · 2023: 14 · 2022: 32 · 2021: 25 · 2020: 28 · 2019: 33 · 2018: 24 · 2017: 21 · 2016: 32 · 2015: 38 · 2014: 45 · 2013: 46 · 2012: 48
FWCI: 41.28
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: microglial activation, amyloid-beta, interferon-gamma, Alzheimer's disease, amyloid plaques, reactive nitrogen intermediates, TNF-α, neuronal injury, neuroinflammation, neurodegeneration
MeSH terms: Aging, Alzheimer Disease, Amino Acid Sequence, Animals, Cells, Cultured, Interferon-gamma, Molecular Sequence Data, Nerve Degeneration, Neuroglia, Nitrogen, Peptide Fragments, Tumor Necrosis Factor-alpha, Amyloid beta-Peptides, Inflammation Mediators, Mice, Rats

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Activation of microglial cells by β-amyloid protein and interferon-γ

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