Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

S100A9-Driven Amyloid-Neuroinflammatory Cascade in Traumatic Brain Injury as a Precursor State for Alzheimer’s Disease

Wang, Chao ; Iashchishyn, Igor A. ; Pansieri, Jonathan ; Nyström, Sofie ; Klementieva, Oxana LU orcid ; Kara, John ; Horvath, Istvan ; Moskalenko, Roman ; Rofougaran, Reza and Gouras, Gunnar LU orcid , et al. (2018) In Scientific Reports 8(1).
Abstract

Pro-inflammatory and amyloidogenic S100A9 protein is an important contributor to Alzheimer’s 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 Aβ 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... (More)

Pro-inflammatory and amyloidogenic S100A9 protein is an important contributor to Alzheimer’s 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 Aβ 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 Aβ. S100A9 and Aβ 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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
8
issue
1
article number
12836
publisher
Nature Publishing Group
external identifiers
  • scopus:85052328156
  • pmid:30150640
ISSN
2045-2322
DOI
10.1038/s41598-018-31141-x
language
English
LU publication?
yes
id
59d83cff-cc47-4b15-b63f-56ee10c0d96c
date added to LUP
2018-09-17 11:06:00
date last changed
2021-10-06 03:05:23
@article{59d83cff-cc47-4b15-b63f-56ee10c0d96c,
  abstract     = {<p>Pro-inflammatory and amyloidogenic S100A9 protein is an important contributor to Alzheimer’s 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 Aβ 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 Aβ. S100A9 and Aβ 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.</p>},
  author       = {Wang, Chao and Iashchishyn, Igor A. and Pansieri, Jonathan and Nyström, Sofie and Klementieva, Oxana and Kara, John and Horvath, Istvan and Moskalenko, Roman and Rofougaran, Reza and Gouras, Gunnar and Kovacs, Gabor G. and Shankar, S. K. and Morozova-Roche, Ludmilla A.},
  issn         = {2045-2322},
  language     = {eng},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {S100A9-Driven Amyloid-Neuroinflammatory Cascade in Traumatic Brain Injury as a Precursor State for Alzheimer’s Disease},
  url          = {http://dx.doi.org/10.1038/s41598-018-31141-x},
  doi          = {10.1038/s41598-018-31141-x},
  volume       = {8},
  year         = {2018},
}