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

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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; Kara, John; Horvath, Istvan; Moskalenko, Roman; Rofougaran, Reza; Gouras, Gunnar; Kovacs, Gabor G.; Shankar, S. K.; Morozova-Roche, Ludmilla A.

I: Scientific Reports, Vol. 8, Nr. 1, 12836, 2018.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Wang, C, Iashchishyn, IA, Pansieri, J, Nyström, S, Klementieva, O, Kara, J, Horvath, I, Moskalenko, R, Rofougaran, R, Gouras, G, Kovacs, GG, Shankar, SK & Morozova-Roche, LA 2018, 'S100A9-Driven Amyloid-Neuroinflammatory Cascade in Traumatic Brain Injury as a Precursor State for Alzheimer’s Disease', Scientific Reports, vol. 8, nr. 1, 12836. https://doi.org/10.1038/s41598-018-31141-x

APA

CBE

Wang C, Iashchishyn IA, Pansieri J, Nyström S, Klementieva O, Kara J, Horvath I, Moskalenko R, Rofougaran R, Gouras G, Kovacs GG, Shankar SK, Morozova-Roche LA. 2018. S100A9-Driven Amyloid-Neuroinflammatory Cascade in Traumatic Brain Injury as a Precursor State for Alzheimer’s Disease. Scientific Reports. 8(1). https://doi.org/10.1038/s41598-018-31141-x

MLA

Vancouver

Author

Wang, Chao ; Iashchishyn, Igor A. ; Pansieri, Jonathan ; Nyström, Sofie ; Klementieva, Oxana ; Kara, John ; Horvath, Istvan ; Moskalenko, Roman ; Rofougaran, Reza ; Gouras, Gunnar ; Kovacs, Gabor G. ; Shankar, S. K. ; Morozova-Roche, Ludmilla A. / S100A9-Driven Amyloid-Neuroinflammatory Cascade in Traumatic Brain Injury as a Precursor State for Alzheimer’s Disease. I: Scientific Reports. 2018 ; Vol. 8, Nr. 1.

RIS

TY - JOUR

T1 - S100A9-Driven Amyloid-Neuroinflammatory Cascade in Traumatic Brain Injury as a Precursor State for Alzheimer’s Disease

AU - Wang, Chao

AU - Iashchishyn, Igor A.

AU - Pansieri, Jonathan

AU - Nyström, Sofie

AU - Klementieva, Oxana

AU - Kara, John

AU - Horvath, Istvan

AU - Moskalenko, Roman

AU - Rofougaran, Reza

AU - Gouras, Gunnar

AU - Kovacs, Gabor G.

AU - Shankar, S. K.

AU - Morozova-Roche, Ludmilla A.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-018-31141-x

DO - 10.1038/s41598-018-31141-x

M3 - Article

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 12836

ER -