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Cited by 27Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsPhagocytosis and Immune Regulation

Effects of Immunomodulatory Substances on Phagocytosis of A by Human Microglia

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Hjorth, Erik, Frenkel, Dan, Weiner, Howard, Schultzberg, Marianne·2010·International Journal of Alzheimer's Disease
DOI 10.4061/2010/798424PMC PMC2925296
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Abstract

Glial activation and increased inflammation characterize neuropathology in Alzheimer's disease (AD). The aim was to develop a model for studying phagocytosis of -amyloid (A) peptide by human microglia and to test effects thereupon by immunomodulatory substances. Human CHME3 microglia showed intracellular A colocalized with lysosome-associated membrane protein-2, indicating phagocytosis. This was increased by interferon-, and to a lesser degree with Protollin, a proteosome-based adjuvant. Secretion of brain-derived neurotrophic factor (BDNF) was decreased by A and by interferon- and interleukin-1. These cytokines, but not A, stimulated interleukin-6 release. Microglia which phagocytosed A exhibited a higher degree of expression of interleukin-1 receptor type I and inducible nitric oxide synthase. In conclusion, we show that human microglia are able to phagocytose A and that this is associated with expression of inflammatory markers. A and interferon- decreased BDNF secretion suggesting a new neuropathological role for A and the inflammation accompanying AD.

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  • In a publicly available patient RNA-seq dataset of microglia from fresh human brain tissue, rs6024870 genotypes were 70 GG, 21 GA, and 2 AA.

    “We identified from the dataset 70 individuals homozygous for the major allele (GG), 21 heterozygous individuals (GA), and only 2 individuals homozygous for the minor allele (AA).”

    From Variant-to-function mapping of late-onset Alzheimer’s disease GWAS signals in human microglial cell models implicates <i>RTFDC1</i> at the <i>CASS4</i> locus (2024) · cites this paper as [58]

    The Materials and Methods (section 2.2, page unavailable) describe experiments with the CHME3 human microglial cell line, not a patient RNA-seq dataset. Searches for rs6024870, the genotype counts, and RNA-seq of fresh human brain tissue found no passage reporting the claimed data. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • In microglia from human brains, rs6024870 acts as an eQTL on RTFDC1 expression, with the minor A allele associated with reduced expression (GG average 93.40 TPM vs GA 85.30 TPM, P=0.0385).

    “and found that GG individuals had on average 93.40 TPM of RTFDC1, significantly higher than GA individuals, which had on average 85.30 TPM (P=0.0385, Student’s 1-tailed T-test, Figure 6C).”

    From Variant-to-function mapping of late-onset Alzheimer’s disease GWAS signals in human microglial cell models implicates <i>RTFDC1</i> at the <i>CASS4</i> locus (2024) · cites this paper as [58]

    The Materials and Methods section (2.9, page unavailable) describes analyses of amyloid-β uptake and cellular markers, not genotype-dependent gene expression. Searches for rs6024870, RTFDC1, eQTL, and the reported TPM values found no passage in our copy addressing the claimed association. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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Authors
Hjorth, E., Frenkel, D., Weiner, H., & Schultzberg, M.
Affiliations
  • Karolinska Institutet (SE)
  • Tel Aviv University (IL)
  • Brigham and Women's Hospital (US)
Corresponding author
Schultzberg, Marianne
ORCID
Venue
International Journal of Alzheimer's Disease
Publisher
Hindawi Limited
Published
2010
Volume
2010
Pages
1-18
ISSN
2090-0252 (ISSN-L)
DOI
10.4061/2010/798424
PMC
PMC2925296
OpenAlex
W1984958202
Cited by
27
References
4
Citations by year
2026: 3 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2020: 1 · 2018: 2 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 6
FWCI
1.68
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Alzheimer s Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Gun och Bertil Stohnes Stiftelse
  • Stiftelsen för Gamla Tjänarinnor
  • Karolinska Institutet
  • Knut och Alice Wallenbergs Stiftelse
  • Stockholms Läns Landsting
  • Vetenskapsrådet (072194)
  • Swedish Brain Power
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords
amyloid-beta, amyloid-beta 42, microglia, phagocytosis, Alzheimer's disease, interferon-gamma, brain-derived neurotrophic factor, IL-1β, interleukin-6, IL1R1, inducible nitric oxide synthase, neuroinflammation, LAMP2

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