Search: onr:"swepub:oai:DiVA.org:uu-500295" >
Long-term effects o...
Long-term effects of amyloid-beta deposits in human iPSC-derived astrocytes
-
- Konstantinidis, Evangelos, 1990- (author)
- Uppsala universitet,Geriatrik
-
- Dakhel, Abdulkhalek (author)
- Uppsala universitet,Geriatrik
-
- Beretta, Chiara (author)
- Uppsala universitet,Geriatrik
-
show more...
-
- Erlandsson, Anna (author)
- Uppsala universitet,Geriatrik
-
show less...
-
(creator_code:org_t)
- Elsevier, 2023
- 2023
- English.
-
In: Molecular and Cellular Neuroscience. - : Elsevier. - 1044-7431 .- 1095-9327. ; 125
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://uu.diva-port... (primary) (Raw object)
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Alzheimer?s disease
- Amyloid beta
- Astrocytes
- Phagocytosis
- Accumulation
- Lysosomes
- Neuroinflammation
- Cytokines
- Reactivity
- Human iPSCs
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database