Myelin loss in C9orf72 hexanucleotide expansion carriers.

Autor: Sirisi S; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Querol-Vilaseca M; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Dols-Icardo O; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Pegueroles J; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Montal V; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Muñoz L; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Torres S; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Ferrer-Raventós P; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Iulita MF; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain., Sánchez-Aced É; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain., Blesa R; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain., Illán-Gala I; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain., Molina-Porcel L; Neurological Tissue Bank of the Biobanc-Hospital Clinic-IDIBAPS, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain., Borrego-Ecija S; Alzheimer's Disease and Other Cognitive Disorders Unit, Service of Neurology, Hospital Clínic, Institut d'Investigació Biomèdica August Pi i Sunyer, University of Barcelona, Barcelona, Spain., Sánchez-Valle R; Neurological Tissue Bank of the Biobanc-Hospital Clinic-IDIBAPS, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.; Alzheimer's Disease and Other Cognitive Disorders Unit, Service of Neurology, Hospital Clínic, Institut d'Investigació Biomèdica August Pi i Sunyer, University of Barcelona, Barcelona, Spain., Clarimon J; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain., Belbin O; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Fortea J; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Lleó A; Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
Jazyk: angličtina
Zdroj: Journal of neuroscience research [J Neurosci Res] 2022 Oct; Vol. 100 (10), pp. 1862-1875. Date of Electronic Publication: 2022 Jun 29.
DOI: 10.1002/jnr.25100
Abstrakt: The most frequent genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) is the hexanucleotide repeat expansion in C9orf72. An important neuropathological hallmark associated with this mutation is the accumulation of the phosphorylated form of TAR (trans-activation response element) DNA-binding protein 43 (pTDP-43). Glia plays a crucial role in the neurodegeneration observed in C9orf72-associated disorders. However, less is known about the role of oligodendrocytes (OLs). Here, we applied digital neuropathological methods to compare the expression pattern of glial cells in the frontal cortex (FrCx) of human post-mortem samples from patients with C9-FTLD and C9-FTLD/ALS, sporadic FTLD (sFTLD), and healthy controls (HCs). We also compared MBP levels in CSF from an independent clinical FTD cohort. We observed an increase in GFAP, and Iba1 immunoreactivity in C9 and sFTLD compared to controls in the gray matter (GM) of the FrCx. We observed a decrease in MBP immunoreactivity in the GM and white matter (WM) of the FrCx of C9, compared to HC and sFTLD. There was a negative correlation between MBP and pTDP-43 in C9 in the WM of the FrCx. We observed an increase in CSF MBP concentrations in C9 and sFTLD compared to HC. In conclusion, the C9 expansion is associated with myelin loss in the frontal cortex. This loss of MBP may be a result of oligodendroglial dysfunction due to the expansion or the presence of pTDP-43 in OLs. Understanding these biological processes will help to identify specific pathways associated with the C9orf72 expansion.
(© 2022 Wiley Periodicals LLC.)
Databáze: MEDLINE
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