ArticleActa neuropathologica communications2017
A data-driven approach links microglia to pathology and prognosis in amyotrophic lateral sclerosis.
Article in Acta neuropathologica communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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Who cites it
52 citing papers in PubMed, 83 citations in OpenAlex.
- Innate immune crosstalk in ALS/FTD pathogenesis.Cell insight · 2026Review
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- Human amyotrophic lateral sclerosis/motor neuron disease: The disease-associated microglial pathway is upregulated while APOE genotype governs risk and survival.Brain pathology (Zurich, Switzerland) · 2025Article
- Is TREM2 a Stretch: Implications of TREM2 Along Spinal Cord Circuits in Health, Aging, Injury, and Disease.Cells · 2025Review
- Review
- Mendelian Randomization and Transcriptome Analyses Reveal Important Roles for CEBPB and CX3CR1 in Osteoarthritis.Bioengineering (Basel, Switzerland) · 2025Article
- Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics.MedComm · 2025Review
- A Review of Biomarkers of Amyotrophic Lateral Sclerosis: A Pathophysiologic Approach.International journal of molecular sciences · 2024Review
- Antibody-mediated targeting of human microglial leukocyte Ig-like receptor B4 attenuates amyloid pathology in a mouse model.Science translational medicine · 2024Article
- Allogenic microglia replacement: A novel therapeutic strategy for neurological disorders.Fundamental research · 2024Review
- A Spleen Tyrosine Kinase's Sky in Neuronal Degeneration.Neuroscience bulletin · 2024Article
- Physical exercise regulates microglia in health and disease.Frontiers in neuroscience · 2024Review
- Decoding sTREM2: its impact on Alzheimer's disease - a comprehensive review of mechanisms and implications.Frontiers in aging neuroscience · 2024Review
- Unsupervised machine learning identifies distinct ALS molecular subtypes in post-mortem motor cortex and blood expression data.Acta neuropathologica communications · 2023Article
- Ameliorative effects of Fingolimod (FTY720) on microglial activation and psychosis-related behavior in short term cuprizone exposed mice.Molecular brain · 2023Article
- Physical activity as an exogenous risk factor for amyotrophic lateral sclerosis: a review of the evidence.Brain : a journal of neurology · 2023Review
- Review
- Neurodegeneration and its potential markers in the diagnosing of secondary progressive multiple sclerosis. A review.Frontiers in molecular neuroscience · 2023Review
- In vitro modelling of human proprioceptive sensory neurons in the neuromuscular system.Scientific reports · 2022Article
- Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that lacks a predictive and broadly applicable biomarker. Continued focus on mutation-specific upstream mechanisms has yet to predict disease progression in the clinic. Utilising cellular pathology common to the majority of ALS patients, we implemented an objective transcriptome-driven approach to develop noninvasive prognostic biomarkers for disease progression. Genes expressed in laser captured motor neurons in direct correlation (Spearman rank correlation, p < 0.01) with counts of neuropathology were developed into co-expression network modules. Screening modules using three gene sets representing rate of disease progression and upstream genetic association with ALS led to the prioritisation of a single module enriched for immune response to motor neuron degeneration. Genes in the network module are important for microglial activation and predict disease progression in genetically heterogeneous ALS cohorts: Expression of three genes in peripheral lymphocytes - LILRA2, ITGB2 and CEBPD - differentiate patients with rapid and slowly progressive disease, suggesting promise as a blood-derived biomarker. TREM2 is a member of the network module and the level of soluble TREM2 protein in cerebrospinal fluid is shown to predict survival when measured in late stage disease (Spearman rank correlation, p = 0.01). Our data-driven systems approach has, for the first time, directly linked microglia to the development of motor neuron pathology. LILRA2, ITGB2 and CEBPD represent peripherally accessible candidate biomarkers and TREM2 provides a broadly applicable therapeutic target for ALS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.