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Altered perivascular fibroblast activity precedes ALS disease onset

Månberg, Anna, 1985- (author)
KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik
Skene, Nathan (author)
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, United Kingdom; United Kingdom Dementia Research Institute, London, United Kingdom
Sanders, Folkert (author)
Department of Clinical Neuroscience, Karolinska Institute, Centre for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
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Trusohamn, Marta (author)
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Remnestål, Julia (author)
KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab
Szczepińska, Anna (author)
Karolinska Institutet
Aksoylu, Inci Sevval (author)
Karolinska Institutet
Lönnerberg, Peter (author)
Karolinska Institutet
Ebarasi, Lwaki (author)
Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
Wouters, Stefan (author)
Department of Clinical Neuroscience, Karolinska Institute, Centre for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
Lehmann, Manuela (author)
Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB)
Olofsson, Jennie (author)
KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik
von Gohren Antequera, Inti (author)
Department of Clinical Neuroscience, Karolinska Institute, Centre for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
Domaniku, Aylin (author)
Department of Clinical Neuroscience, Karolinska Institute, Centre for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
De Schaepdryver, Maxim (author)
Laboratory for Neurobiomarker Research, Department of Neurology, Leuven Brain Institute, KU Leuven (University of Leuven), Leuven, Belgium
De Vocht, Joke (author)
Neurology Department and Center for Brain & Disease Research, KU Leuven, VIB, Leuven, Belgium
Poesen, Koen (author)
Laboratory for Neurobiomarker Research, Department of Neurology, Leuven Brain Institute, KU Leuven (University of Leuven), Leuven, Belgium; Laboratory Medicine, UZ Leuven (University Hospital Leuven), Leuven, Belgium
Uhlén, Mathias (author)
KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
Anink, Jasper (author)
Department of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, Netherlands
Mijnsbergen, Caroline (author)
Department of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, Netherlands
Vergunst-Bosch, Hermieneke (author)
UMC Utrecht Brain Center, University Medical Center Utrecht, Department of Neurology, Utrecht University, Utrecht, Netherlands
Hübers, Annemarie (author)
University of Ulm, Neurology Clinic, Ulm, Germany; Division of Neurology, Geneva University Hospital, Geneva, Switzerland
Kläppe, Ulf (author)
Karolinska Institutet
Rodriguez-Vieitez, Elena (author)
Karolinska Institutet
Gilthorpe, Jonathan D. (author)
Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB)
Hedlund, Eva (author)
Karolinska Institutet
Harris, Robert A. (author)
Karolinska Institutet
Aronica, Eleonora (author)
Department of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, Netherlands
Van Damme, Philip (author)
Neurology Department and Center for Brain & Disease Research, KU Leuven, VIB, Leuven, Belgium
Ludolph, Albert (author)
University of Ulm, Neurology Clinic, Ulm, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ulm, Bonn, Germany
Veldink, Jan (author)
UMC Utrecht Brain Center, University Medical Center Utrecht, Department of Neurology, Utrecht University, Utrecht, Netherlands
Ingre, Caroline (author)
Karolinska Institutet
Nilsson, Peter (author)
KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik
Lewandowski, Sebastian (author)
KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab,Department of Clinical Neuroscience, Karolinska Institute, Centre for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
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 (creator_code:org_t)
2021-04-15
2021
English.
In: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 27:4, s. 640-646
Related links:
http://spiral.imperi...
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Apart from well-defined factors in neuronal cells1, only a few reports consider that the variability of sporadic amyotrophic lateral sclerosis (ALS) progression can depend on less-defined contributions from glia2,3 and blood vessels4. In this study we use an expression-weighted cell-type enrichment method to infer cell activity in spinal cord samples from patients with sporadic ALS and mouse models of this disease. Here we report that patients with sporadic ALS present cell activity patterns consistent with two mouse models in which enrichments of vascular cell genes preceded microglial response. Notably, during the presymptomatic stage, perivascular fibroblast cells showed the strongest gene enrichments, and their marker proteins SPP1 and COL6A1 accumulated in enlarged perivascular spaces in patients with sporadic ALS. Moreover, in plasma of 574 patients with ALS from four independent cohorts, increased levels of SPP1 at disease diagnosis repeatedly predicted shorter survival with stronger effect than the established risk factors of bulbar onset or neurofilament levels in cerebrospinal fluid. We propose that the activity of the recently discovered perivascular fibroblast can predict survival of patients with ALS and provide a new conceptual framework to re-evaluate definitions of ALS etiology.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

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