Microglial activation correlates with disease progression and upper motor neuron clinical symptoms in amyotrophic lateral sclerosis.
Johannes Brettschneider,Johannes Brettschneider,Jon B. Toledo,Vivianna M. Van Deerlin,Lauren Elman,Leo McCluskey,Virginia M.-Y. Lee,John Q. Trojanowski +7 more
TLDR
This study demonstrates that microglial pathology in the CST of ALS correlates with disease progression and is linked to severity of UMN deficits.Abstract:
Background/Aims: We evaluated clinicopathological correlates of upper motor neuron (UMN) damage in amyotrophic lateral sclerosis (ALS), and analyzed if the presence of the C9ORF72 repeat expansion was associated with alterations in microglial inflammatory activity. Methods: Microglial pathology was assessed by IHC with 2 different antibodies (CD68, Iba1), myelin loss by Kluver-Barrera staining and myelin basic protein (MBP) IHC, and axonal loss by neurofilament protein (TA51) IHC, performed on 59 autopsy cases of ALS including 9 cases with C9ORF72 repeat expansion. Results: Microglial pathology as depicted by CD68 and Iba1 was significantly more extensive in the corticospinal tract (CST) of ALS cases with a rapid progression of disease. Cases with C9ORF72 repeat expansion showed more extensive microglial pathology in the medulla and motor cortex which persisted after adjusting for disease duration in a logistic regression model. Higher scores on the clinical UMN scale correlated with increasing microglial pathology in the cervical CST. TDP-43 pathology was more extensive in the motor cortex of cases with rapid progression of disease. Conclusions: This study demonstrates that microglial pathology in the CST of ALS correlates with disease progression and is linked to severity of UMN deficits.read more
Citations
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Innate immune activation in neurodegenerative disease
TL;DR: How the activation of innate immune signalling pathways — in particular, the NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome — by aberrant host proteins may be a common step in the development of diverse neurodegenerative disorders is discussed.
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Inflammation and white matter degeneration persist for years after a single traumatic brain injury
Victoria E. Johnson,Janice Stewart,Janice Stewart,Finn D. Begbie,John Q. Trojanowski,Douglas H. Smith,William Stewart,William Stewart +7 more
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Daniel Sommermeyer,Michael Hudecek,Michael Hudecek,Paula L. Kosasih,Tea Gogishvili,David G. Maloney,David G. Maloney,Cameron J. Turtle,Cameron J. Turtle,Stanley R. Riddell,Stanley R. Riddell,Stanley R. Riddell +11 more
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Chronic neuropathologies of single and repetitive TBI: substrates of dementia?
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Microglia-mediated neuroinflammation in neurodegenerative diseases.
TL;DR: This review gives a detailed account of the microglia-mediated neuroinflammation in various neurodegenerative diseases and shows great promise as a novel treatment strategy to reduce neuronal damage and to foster a permissive environment for further regeneration effort.
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Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
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Interrater Reliability of a Modified Ashworth Scale of Muscle Spasticity
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El Escorial revisited : revised criteria for the diagnosis of amyotrophic lateral sclerosis
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Journal ArticleDOI
Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS
Mariely DeJesus-Hernandez,Ian R. A. Mackenzie,Bradley F. Boeve,Adam L. Boxer,Matt Baker,Nicola J. Rutherford,Alexandra M. Nicholson,Ni Cole A. Finch,Heather C. Flynn,Jennifer Adamson,Naomi Kouri,Aleksandra Wojtas,Pheth Sengdy,Ging-Yuek Robin Hsiung,Anna Karydas,William W. Seeley,Keith A. Josephs,Giovanni Coppola,Daniel H. Geschwind,Zbigniew K. Wszolek,Howard Feldman,Howard Feldman,David S. Knopman,Ronald C. Petersen,Bruce L. Miller,Dennis W. Dickson,Kevin B. Boylan,Neill R. Graff-Radford,Rosa Rademakers +28 more
TL;DR: It is found that repeat expansion in C9ORF72 is a major cause of both FTD and ALS, suggesting multiple disease mechanisms.
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