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Cited by 68Extracellular vesicles in diseaseAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

Increased Release of Apolipoprotein E in Extracellular Vesicles Following Amyloid-β Protofibril Exposure of Neuroglial Co-Cultures

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Nikitidou, Elisabeth, Khoonsari, Payam Emami, Shevchenko, Ganna, Ingelsson, Martin, Kultima, Kim, Erlandsson, Anna·2017·Journal of Alzheimer's Disease
DOI 10.3233/jad-170278PMC PMC5676865
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Abstract

Extracellular vesicles (EVs), including exosomes and larger microvesicles, have been implicated to play a role in several conditions, including Alzheimer's disease (AD). Since the EV content mirrors the intracellular environment, it could contribute with important information about ongoing pathological processes and may be a useful source for biomarkers, reflecting the disease progression. The aim of the present study was to analyze the protein content of EVs specifically released from a mixed co-culture of primary astrocytes, neurons, and oligodendrocytes treated with synthetic amyloid-β (Aβ42) protofibrils. The EV isolation was performed by ultracentrifugation and validated by transmission electron microscopy. Mass spectrometry analysis of the EV content revealed a total of 807 unique proteins, of which five displayed altered levels in Aβ42 protofibril exposed cultures. The most prominent protein was apolipoprotein E (apoE), and by western blot analysis we could confirm a threefold increase of apoE in EVs from Aβ42 protofibril exposed cells, compared to unexposed cells. Moreover, immunoprecipitation studies demonstrated that apoE was primarily situated inside the EVs, whereas immunocytochemistry indicated that the EVs most likely derived from the astrocytes and the neurons in the culture. The identified Aβ-induced sorting of apoE into EVs from cultured neuroglial cells suggests a possible role for intercellular transfer of apoE in AD pathology and encourage future studies to fully elucidate the clinical relevance of this event.

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  • ApoE, mainly a plasma lipoprotein component, can also exist in non-lipidated form and within EVs.

    “ApoE, mainly a plasma lipoprotein component, 55 can also exist in non‐lipidated form and within EVs. 56 , 57”

    From Plasma extracellular vesicles from <i>APOE3</i> Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease (2026) · cites this paper as [57]

    The Results section ('Apolipoprotein E is primarily situated inside isolated EVs'; page unavailable) confirms that apoE can occur within extracellular vesicles. The paper does not establish that apoE can exist in non-lipidated form; its observation of some apoE outside intact EVs does not determine whether that apoE is lipidated. The plasma-lipoprotein description is attached to a different citation in the citing sentence. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The concentrations of αSYN-F and Aβ-F used were selected based on previous studies.

    “The concentrations were selected based on our previous studies [11, 12, 23, 28, 29].”

    From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [29]

    The Materials and Methods sections on synthetic Aβ42 protofibrils and Aβ42 protofibril exposure describe a previously established preparation protocol and report a 0.1 μM exposure concentration. They do not say that this concentration was selected based on previous studies, and the searched passages do not address selection of an αSYN-F concentration. (LLM, conf=0.72)

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References 65 · Cited by 68

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Authors
Nikitidou, E., Khoonsari, P. E., Shevchenko, G., Ingelsson, M., Kultima, K., & Erlandsson, A.
Affiliations
Uppsala University (SE)
Corresponding author
Erlandsson, Anna
ORCID
Venue
Journal of Alzheimer's Disease
Publisher
SAGE Publications
Published
2017-08-29
Volume
60
Issue
1
Pages
305-321
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-170278
PMC
PMC5676865
OpenAlex
W2745492316
Cited by
68
References
65
Citations by year
2026: 7 · 2025: 4 · 2024: 6 · 2023: 19 · 2022: 12 · 2021: 6 · 2020: 4 · 2019: 8 · 2018: 1 · 2017: 1
FWCI
1.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Alzheimer s Disease (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
Funders
  • Åke Wiberg Stiftelse
  • Petrus och Augusta Hedlunds Stiftelse
  • Vetenskapsrådet
  • Åhlén-stiftelsen
  • Uppsala Universitet
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
apolipoprotein E, extracellular vesicles
MeSH terms
Extracellular Vesicles, Animals, Apolipoproteins E, Cell Count, Cells, Cultured, Embryo, Mammalian, Mice, Inbred C57BL, Nerve Tissue Proteins, Neuroglia, Neurons, Peptide Fragments, Proteins, Mass Spectrometry, Time Factors, Tubulin, 2',3'-Cyclic-Nucleotide Phosphodiesterases, Amyloid beta-Peptides, Coculture Techniques, Microscopy, Electron, Transmission, Mice

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