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Cited by 90Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsMicroRNA in disease regulation

Spreading of Alzheimer’s disease inflammatory signaling through soluble micro-RNA

Open access
Lukiw, Walter J., Alexandrov, Peter N., Zhao, Yuhai, Hill, James M., Bhattacharjee, Surjyadipta·2012·NeuroReport
DOI 10.1097/wnr.0b013e32835542b0PMC PMC4467540
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Abstract

Alzheimer's disease is a progressive, neurodegenerative disorder that develops within the limbic system, spreading radially into anatomically linked brain association areas as the disease progresses. Analysis of temporal-lobe association of neocortex-derived extracellular fluid and cerebrospinal fluid from Alzheimer's disease patients shows an abundant presence of micro-RNA (miRNA), including the proinflammatory miRNA-146a and miRNA-155. Using a novel and highly sensitive LED-Northern dot-blot focusing technique, we detected the secretion of potentially pathogenic amounts of miRNA-146a and miRNA-155 from stressed human primary neural cells. A conditioned medium containing miRNA-146a and miRNA-155 was found to induce Alzheimer-type gene expression changes in control brain cells. These included downregulation in the expression of an important repressor of the innate immune response, complement factor H (CFH). These effects were neutralized using anti-miRNA strategies. Anti-miRNA-based therapeutics may provide a novel and efficacious treatment to stem the miRNA-mediated spreading of inflammatory signaling involved in Alzheimer's disease.

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  • Expression of the pro-inflammatory miRNA miR-155 is increased in the AD brain.

    “Expression of the pro-inflammatory miRNA, miR-155, is increased in the AD brain.”

    From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [17]

    The Results section ('Upregulation of miRNA-146a and miRNA-155 in Alzheimer’s disease ECF and CSF'; page not provided) reports increased pro-inflammatory miR-155 in neocortical extracellular fluid and cerebrospinal fluid from Alzheimer’s disease patients versus age-matched controls. It does not establish increased miR-155 expression throughout AD brain tissue, as the citing sentence could imply. (LLM, conf=0.82)

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Cites

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Research works printed but not linked: 24

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Cited by

Sorted by citations

Authors
Lukiw, W. J., Alexandrov, P. N., Zhao, Y., Hill, J. M., & Bhattacharjee, S.
Affiliations
  • Louisiana State University (US)
  • The University of Texas Health Science Center at Houston (US)
  • Louisiana State University Health Sciences Center New Orleans (US)
Corresponding author
Lukiw, Walter J.
ORCID
Venue
NeuroReport
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2012-07
Volume
23
Issue
10
Pages
621-626
ISSN
0959-4965 (ISSN-L)
DOI
10.1097/wnr.0b013e32835542b0
PMC
PMC4467540
OpenAlex
W2026348014
Cited by
90
References
1
Citations by year
2026: 1 · 2024: 4 · 2023: 5 · 2022: 2 · 2021: 11 · 2020: 5 · 2019: 4 · 2018: 9 · 2017: 8 · 2016: 6 · 2015: 10 · 2014: 7 · 2013: 16 · 2012: 2
FWCI
5.64
Type
journal article
Language
en
Open access
Locations
  • Neuroreport (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (P50 AG 16573, AG038834, P50AG016573, AG18031, R01AG038834, R01AG018031)
  • National Eye Institute (R01EY006311)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
Alzheimer's disease, microRNA, miRNA-146a, miR-155, neuroinflammation, cerebrospinal fluid, conditioned medium, complement factor H, innate immune response, neurodegeneration
MeSH terms
Alzheimer Disease, Brain, Humans, Solubility, Signal Transduction, Culture Media, Conditioned, Inflammation Mediators, Coculture Techniques, MicroRNAs

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