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Oligomeric amyloid-...
Oligomeric amyloid-beta induces early and widespread changes to the proteome in human iPSC-derived neurons
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- Sackmann, Christopher, 1988- (author)
- Linköpings universitet,Avdelningen för neurobiologi,Medicinska fakulteten,Region Östergötland, Klinisk patologi
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- Hallbeck, Martin, 1970- (author)
- Linköpings universitet,Avdelningen för neurobiologi,Medicinska fakulteten,Region Östergötland, Klinisk patologi
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(creator_code:org_t)
- 2020-04-16
- 2020
- English.
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Abstract
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- Alzheimer’s disease (AD) is the most common form of dementia globally and is characterized by aberrant accumulations of amyloid-beta (Aβ) and tau proteins. Oligomeric forms of these proteins are believed to be most relevant to disease progression, with oligomeric amyloid-β (oAβ) particularly implicated in AD. oAβ pathology spreads among interconnected brain regions, but how oAβ induces pathology in these previously unaffected neurons requires further study. Here, we use well characterized iPSC-derived human neurons to study the early changes to the proteome and phosphoproteome after 24 h exposure to oAβ 1-42. Using nLC-MS/MS and label-free quantification, we identified several proteins that are differentially regulated in response to acute oAβ challenge. At this early timepoint, oAβ induced the decrease of TDP-43, heterogeneous nuclear ribonucleoproteins (hnRNPs), and coatomer complex I (COPI) proteins. Conversely, increases were observed in 20 S proteasome subunits and vesicle associated proteins VAMP1/2, as well as the differential phosphorylation of tau at serine 208. These changes show that there are widespread alterations to the neuronal proteome within 24 h of oAβ uptake, including proteins previously not shown to be related to neurodegeneration. This study provides new targets for the further study of early mediators of AD pathogenesis.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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