liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • 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
S100A9-Driven Amyloid-Neuroinflammatory Cascade in Traumatic Brain Injury as a Precursor State for Alzheimers Disease
Umeå Univ, Sweden.
Umeå Univ, Sweden; Sumy State Univ, Ukraine.
Umeå Univ, Sweden.
Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0002-4303-4783
Show others and affiliations
2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 12836Article in journal (Refereed) Published
Abstract [en]

Pro-inflammatory and amyloidogenic S100A9 protein is an important contributor to Alzheimers disease (AD) pathology. Traumatic brain injury (TBI) is viewed as a precursor state for AD. Here we have shown that S100A9-driven amyloid-neuroinflammatory cascade was initiated in TBI and may serve as a mechanistic link between TBI and AD. By analyzing the TBI and AD human brain tissues, we demonstrated that in post-TBI tissues S100A9, produced by neurons and microglia, becomes drastically abundant compared to A beta and contributes to both precursor-plaque formation and intracellular amyloid oligomerization. Conditions implicated in TBI, such as elevated S100A9 concentration, acidification and fever, provide strong positive feedback for S100A9 nucleation-dependent amyloid formation and delay in its proteinase clearance. Consequently, both intracellular and extracellular S100A9 oligomerization correlated with TBI secondary neuronal loss. Common morphology of TBI and AD plaques indicated their similar initiation around multiple aggregation centers. Importantly, in AD and TBI we found S100A9 plaques without A beta. S100A9 and A beta plaque pathology was significantly advanced in AD cases with TBI history at earlier age, signifying TBI as a risk factor. These new findings highlight the detrimental consequences of prolonged post-TBI neuroinflammation, which can sustain S100A9-driven amyloid-neurodegenerative cascade as a specific mechanism leading to AD development.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2018. Vol. 8, article id 12836
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-151504DOI: 10.1038/s41598-018-31141-xISI: 000442870300014PubMedID: 30150640OAI: oai:DiVA.org:liu-151504DiVA, id: diva2:1250630
Note

Funding Agencies|ALF Vasterbotten Lans Landsting; Swedish Medical Research Council; FP-7 Marie Curie Action "Nano-Guard"; Insamlingsstiftelsen; Swedish Alzheimers Foundation; Swedish Institute

Available from: 2018-09-24 Created: 2018-09-24 Last updated: 2019-11-08

Open Access in DiVA

fulltext(6015 kB)61 downloads
File information
File name FULLTEXT01.pdfFile size 6015 kBChecksum SHA-512
fdd7e3b72efbc1fa2884871df819f5b7c7186f34a64e758e590f8b35f2acc8fc7c5f4bc3ec53acb1ae8f93be0f8ec4629ccc4b6f91d6b8d9c9774adfec14720d
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Nyström, Sofie
By organisation
ChemistryFaculty of Science & Engineering
In the same journal
Scientific Reports
Neurosciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 61 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: 42 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • 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