Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Long-term effects of amyloid-beta deposits in human iPSC-derived astrocytes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.ORCID iD: 0000-0002-8753-347x
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.ORCID iD: 0000-0002-5817-9547
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.ORCID iD: 0000-0001-7292-1608
2023 (English)In: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 125, article id 103839Article in journal (Refereed) Published
Abstract [en]

Growing evidence indicates that astrocytes are tightly connected to Alzheimer's disease (AD) pathogenesis. However, the way in which astrocytes participate in AD initiation and progression remains to be clarified. Our previous data show that astrocytes engulf large amounts of aggregated amyloid-beta (A beta) but are unable to successfully degrade the material. In this study, we aimed to evaluate how intracellular A beta-accumulation affects the astrocytes over time. For this purpose, human induced pluripotent cell (hiPSC)-derived astrocytes were exposed to sonicated A beta-fibrils and then cultured further for one week or ten weeks in A beta-free medium. Cells from both time points were analyzed for lysosomal proteins and astrocyte reactivity markers and the media were screened for inflammatory cytokines. In addition, the overall health of cytoplasmic organelles was investigated by immunocytochemistry and electron microscopy. Our data demonstrate that long-term astrocytes retained frequent A beta-inclusions that were enclosed within LAMP1-positive organelles and sustained markers associated with reactivity. Furthermore, A beta-accumulation resulted in endoplasmic reticulum and mitochondrial swelling, increased secretion of the cytokine CCL2/MCP-1 and formation of pathological lipid structures. Taken together, our results provide valuable information of how intracellular A beta-deposits affect astrocytes, and thereby contribute to the understanding of the role of astrocytes in AD progression.

Place, publisher, year, edition, pages
Elsevier, 2023. Vol. 125, article id 103839
Keywords [en]
Alzheimer?s disease, Amyloid beta, Astrocytes, Phagocytosis, Accumulation, Lysosomes, Neuroinflammation, Cytokines, Reactivity, Human iPSCs
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-500295DOI: 10.1016/j.mcn.2023.103839ISI: 000957221400001PubMedID: 36907531OAI: oai:DiVA.org:uu-500295DiVA, id: diva2:1753040
Funder
Swedish Research Council, 2021-02563Available from: 2023-04-25 Created: 2023-04-25 Last updated: 2023-04-25Bibliographically approved

Open Access in DiVA

fulltext(12150 kB)172 downloads
File information
File name FULLTEXT01.pdfFile size 12150 kBChecksum SHA-512
85d4e1897635a67d6a251eb572e523d77fd952834112544ea46ad54f475fb314ab945daf3c9f17cc1abe5cb5eac3e41fe010271e6fd17f787313e031e1cf329f
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records

Konstantinidis, EvangelosDakhel, AbdulkhalekBeretta, ChiaraErlandsson, Anna

Search in DiVA

By author/editor
Konstantinidis, EvangelosDakhel, AbdulkhalekBeretta, ChiaraErlandsson, Anna
By organisation
Geriatrics
In the same journal
Molecular and Cellular Neuroscience
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 173 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 138 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf