Cited by 268Amyotrophic Lateral Sclerosis ResearchNeuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatments

Microglial Activation Correlates with Disease Progression and Upper Motor Neuron Clinical Symptoms in Amyotrophic Lateral Sclerosis

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Brettschneider, Johannes, Toledo, Jon B., Van Deerlin, Vivianna M., Elman, Lauren, McCluskey, Leo, Lee, Virginia M.-Y., Trojanowski, John Q.·2012·PLoS ONE

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.

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Crossref · 10.1371/journal.pone.0039216

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  • ALS patients carrying C9orf72 mutations display microglial activation that correlates with disease progression.

    “ALS patients carrying C9orf72 mutations display microglial activation that correlates with disease progression [438].”
  • Postmortem and in vivo PET studies revealed widespread cerebral microglial activation in patients with ALS and even in pre-symptomatic ALS-related mutation carriers.

    “Postmortem studies308–310 and in vivo PET studies311–313 revealed widespread cerebral microglial activation in patients with ALS,308–312 and even in pre-symptomatic ALS-related mutation carriers.309,313”
  • Microglial activation in the corticospinal tract of ALS correlated with neuronal and axonal loss and more severe upper motor neuron symptoms.

    “Microglial activation in the corticospinal tract of ALS correlated with neuronal and axonal loss and more severe upper motor neuron symptoms.309”
  • Decreased C9orf72 expression in C9-ALS led to altered microglial function and increased microglial activation.

    “Transcriptome and histologic analyses of postmortem tissue from patients with ALS carrying the C9orf72 expansion (C9-ALS) found that decreased C9orf72 expression in C9-ALS led to altered microglial function and increased microglial activation.309,361”

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Authors
Brettschneider, J., Toledo, J. B., Van Deerlin, V. M., Elman, L., McCluskey, L., Lee, V. M.-Y., & Trojanowski, J. Q.
Affiliations
  • Universität Ulm (DE)
  • University of Pennsylvania (US)
Corresponding author
Brettschneider, Johannes
Venue
PLoS ONE
Published
2012-06-14
Volume
7
Issue
6
Pages
e39216
ISSN
1932-6203 (ISSN-L)
OpenAlex
W1974485241
Cited by
268
References
68
Citations by year
2026: 16 · 2025: 18 · 2024: 23 · 2023: 27 · 2022: 24 · 2021: 25 · 2020: 24 · 2019: 24 · 2018: 15 · 2017: 22 · 2016: 10 · 2015: 13 · 2014: 12 · 2013: 13 · 2012: 2
FWCI
8.26
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Deutsche Forschungsgemeinschaft (AG10124)
  • National Institutes of Health (AG 10 124, AG 17586)
  • National Institute on Aging (AG033101, AG-32953, P30AG010124, P01AG017586, AG17586, AG-10124, K08AG033101, P01AG032953)
Topics
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
amyotrophic lateral sclerosis, microglial activation, upper motor neuron lesion, corticospinal tract, C9orf72 repeat expansion, disease progression, TDP-43 pathology, demyelination, axonal loss, neuroinflammation, motor cortex, medulla
MeSH terms
Aged, Amyotrophic Lateral Sclerosis, Axons, Base Sequence, Female, Humans, Male, Middle Aged, Motor Neurons, Cohort Studies, Polymerase Chain Reaction, Open Reading Frames, Microglia, DNA Primers, Disease Progression

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