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

Scientific Reports
Chao WangLudmilla A Morozova-Roche

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 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 fact...Continue Reading

References

Apr 1, 1994·Journal of Neurology, Neurosurgery, and Psychiatry·G W RobertsD I Graham
Dec 9, 1998·Acta Neuropathologica·H J SchluesenerR Meyermann
May 4, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·R S ClarkS H Graham
Jan 17, 2002·The New England Journal of Medicine·B A in t' VeldB H Stricker
Feb 8, 2002·Molecular Neurobiology·A G Yakovlev, A I Faden
Mar 20, 2003·Microscopy Research and Technique·Wolfgang NackenClaus Kerkhoff
Jan 1, 1962·Journal of Molecular Biology·F OOSAWA, M KASAI
Jul 16, 2004·Journal of Neurotrauma·Arun K GuptaDavid K Menon
Oct 12, 2004·Experimental Neurology·Milos D IkonomovicSteven T DeKosky
Feb 8, 2005·Critical Care : the Official Journal of the Critical Care Forum·Xiaopeng ZhangRobert S B Clark
Oct 29, 2005·Neurobiology of Aging·C E ShepherdG M Halliday
Oct 20, 2006·Biochimica Et Biophysica Acta·Thomas VoglJohannes Roth
May 15, 2009·PloS One·Kiran YanamandraLudmilla A Morozova-Roche
Nov 17, 2009·Journal of Molecular Biology·Mantas MalisauskasLudmilla Morozova-Roche
Jan 12, 2010·Journal of Alzheimer's Disease : JAD·Edith G McGeer, Patrick L McGeer
Feb 5, 2010·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Bogdan A Stoica, Alan I Faden
Mar 9, 2010·CNS & Neurological Disorders Drug Targets·Greg M Cole, Sally A Frautschy
Mar 11, 2010·Nature Reviews. Neuroscience·Victoria E JohnsonDouglas H Smith
May 28, 2010·Journal of Neurotrauma·Brent E Masel, Douglas S DeWitt
Mar 7, 2012·Neuroscience and Biobehavioral Reviews·Thamil Mani Sivanandam, Mahendra Kumar Thakur
Apr 11, 2012·International Journal of Molecular Sciences·Thomas VoglLudmilla A Morozova-Roche
Jun 26, 2012·Brain, Behavior, and Immunity·Alok Kumar, David J Loane
Oct 19, 2012·The Journal of Biological Chemistry·Hugo M BotelhoCláudio M Gomes
Dec 12, 2012·Neuron·Kaj BlennowHenrik Zetterberg
Feb 7, 2013·Scientific Reports·William R SwindellJohann E Gudjonsson
Mar 6, 2013·Nature Reviews. Neurology·Douglas H SmithWilliam Stewart
May 15, 2013·Cell Metabolism·Prabhakara R NagareddyIra J Goldberg
Jul 23, 2013·Frontiers in Aging Neuroscience·Joshua J BreunigTerrence Town
Nov 19, 2013·Acta Neuropathologica·Chao WangLudmilla A Morozova-Roche
Aug 8, 2014·Nature Communications·Thomas VoglJohannes Roth
Jan 24, 2015·Nature Reviews. Cancer·Anne R BresnickDanna B Zimmer

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Citations

Dec 14, 2018·Frontiers in Aging Neuroscience·Xingyu ZhangZhentao Zhang
Apr 25, 2020·International Journal of Molecular Sciences·Adriana Kubis-KubiakAgnieszka Piwowar
Jun 4, 2019·Frontiers in Neuroscience·Joana S Cristóvão, Cláudio M Gomes
Apr 4, 2021·International Journal of Molecular Sciences·Mehdi EshraghiSaeid Ghavami
Jun 3, 2021·International Journal of Molecular Sciences·Kazutoshi KashoSjoerd Wanrooij
Jun 14, 2019·ACS Chemical Biology·Jonathan PansieriLudmilla A Morozova-Roche
Aug 28, 2021·International Journal of Molecular Sciences·Lili ArabuliLudmilla A Morozova-Roche

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Methods Mentioned

BETA
transgenic
AFM
atomic force microscopy
Fluorescence
confocal microscopy
fluorescence imaging
fluorescence microscopy

Software Mentioned

Imaris

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