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Kara, John
Publications (3 of 3) Show all publications
Wang, C., Iashchishyn, I., Kara, J., Fodera, V., Vetri, V., Sancataldo, G., . . . Morozova-Roche, L. (2019). Proinflammatory and amyloidogenic S100A9 induced by traumatic brain injury in mouse model. Neuroscience Letters, 699, 199-205
Open this publication in new window or tab >>Proinflammatory and amyloidogenic S100A9 induced by traumatic brain injury in mouse model
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2019 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 699, p. 199-205Article in journal (Refereed) Published
Abstract [en]

Traumatic brain injury (TBI) represents a significant risk factor for development of neurodegenerative diseases such as Alzheimer's and Parkinson's. The S100A9-driven amyloid-neuroinflammatory cascade occurring during primary and secondary TBI events can serve as a mechanistic link between TBI and Alzheimer's as demonstrated recently in the human brain tissues. Here by using immunohistochemistry in the controlled cortical impact TBI mouse model we have found pro-inflammatory S100A9 in the brain tissues of all mice on the first and third post- TBI days, while 70% of mice did not show any S100A9 presence on seventh post-TBI day similar to controls. This indicates that defensive mechanisms effectively cleared S100A9 in these mouse brain tissues during post-TBI recovery. By using sequential immunohistochemistry we have shown that S100A9 was produced by both neuronal and microglial cells. However, A beta peptide deposits characteristic for Alzheimer's disease were not detected in any post-TBI animals. On the first and third post-TBI days S100A9 was found to aggregate intracellularly into amyloid oligomers, similar to what was previously observed in human TBI tissues. Complementary, by using Rayleigh scatting, intrinsic fluorescence and atomic force microscopy we demonstrated that in vitro S100A9 self- assembles into amyloid oligomers within minutes. Its amyloid aggregation is highly dependent on changes of environmental conditions such as variation of calcium levels, pH, temperature and reduction/oxidation, which might be relevant to perturbation of cellular and tissues homeostasis under TBI. Present results demonstrate that S100A9 induction mechanisms in TBI are similar in mice and humans, emphasizing that S100A9 is an important marker of brain injury and therefore can be a potential therapeutic target.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2019
Keywords
Alzheimer's disease, Amyloid, Neuroinflammation, Oligomerization, S100A9, Traumatic brain injury
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-158949 (URN)10.1016/j.neulet.2019.02.012 (DOI)000465055200032 ()30753908 (PubMedID)
Available from: 2019-05-27 Created: 2019-05-27 Last updated: 2019-05-27Bibliographically approved
Wang, C., Iashchishyn, I., Pansieri, J., Nyström, S., Klementieva, O., Kara, J., . . . Morozova-Roche, L. (2018). S100A9-Driven Amyloid-Neuroinflammatory Cascade in Traumatic Brain Injury as a Precursor State for Alzheimer's Disease. Scientific Reports, 8, Article ID 12836.
Open this publication in new window or tab >>S100A9-Driven Amyloid-Neuroinflammatory Cascade in Traumatic Brain Injury as a Precursor State for Alzheimer's Disease
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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 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 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
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-151784 (URN)10.1038/s41598-018-31141-x (DOI)000442870300014 ()30150640 (PubMedID)
Funder
Swedish Institute
Available from: 2018-09-14 Created: 2018-09-14 Last updated: 2018-09-14Bibliographically approved
Wang, C., Iashchishyn, I., Nyström, S., Klementieva, O., Kara, J., Bengtsson, S., . . . Morozova-Roche, L.S100A9-driven amyloid-neuroinflammatory cascade in traumatic brain injury as a risk factor for Alzheimer’s disease.
Open this publication in new window or tab >>S100A9-driven amyloid-neuroinflammatory cascade in traumatic brain injury as a risk factor for Alzheimer’s disease
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(English)Manuscript (preprint) (Other academic)
Keywords
Traumatic brain injury, Alzheimer’s disease, Aβ, S100A9, Amyloid, Cytotoxicity; Neuroinflammation
National Category
Other Medical Sciences not elsewhere specified
Research subject
Medical Biochemistry
Identifiers
urn:nbn:se:umu:diva-125077 (URN)
External cooperation:
Projects
Role of pro-inflammatory S100A9 protein in amyloid-neuroinflammatory cascade in Alzheimer’s disease and traumatic brain injury
Available from: 2016-09-05 Created: 2016-09-05 Last updated: 2018-06-07
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