SynthesisNeurobiology of disease2021
Systematic review and meta-analysis of human transcriptomics reveals neuroinflammation, deficient energy metabolism, and proteostasis failure across neurodegeneration.
Synthesis in Neurobiology of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 90 citations in OpenAlex.
- Meta-Analysis of Transcriptomic Studies of Blood and Six Brain Regions Identifies a Consensus of 15 Cross-Tissue Mechanisms in Alzheimer's Disease and Suggests an Origin of Cross-Study Heterogeneity.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2025Pooled it
- Differentially Expressed miRNAs in Age-Related Neurodegenerative Diseases: A Meta-Analysis.Genes · 2022Pooled it
- Insights Into the Role of Platelet Factor 4 in Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2026Review
- CSF Leukocytes Transiently Increase Before Onset of Huntington Disease in Association With a Stage-Specific CSF Cytokine/Chemokine Pattern.Neurology(R) neuroimmunology & neuroinflammation · 2026Observational
- Alzheimer's Disease as a Multi-Layer Network Disorder: A Systems Biology Framework Integrating Multi-Omics Mechanisms.Biomedicines · 2026Review
- Application of the Allen Human Brain Atlas in Alzheimer's disease and Parkinson's disease.Translational neurodegeneration · 2026Review
- Plasma-Derived miRNAs as Fluid Biomarkers to Differentiate Alzheimer's and Frontotemporal Dementia.Current issues in molecular biology · 2026Article
- Integrative Transcriptomic, Network, and Machine Learning Analyses Identify Genistein and Resveratrol-Associated Therapeutic Targets in Alzheimer's Disease.Molecular neurobiology · 2026Article
- Systems genetic dissection of brain gene expression reveals excitotoxic mechanisms of Alzheimer's disease.Molecular psychiatry · 2026Article
- Reimagining GSK-3β Therapeutics in Alzheimer's Disease: From Inhibition to Activity Normalization and Targeted Degradation.Journal of molecular neuroscience : MN · 2026Review
- Insights and priorities from the 2025 private funders' Parkinson's disease and related disorders large footprint data interoperability summit.Journal of Parkinson's disease · 2026Article
- Potential common pathogenesis of several neurodegenerative diseases.Neural regeneration research · 2026Article
- Understanding Neurodegenerative Diseases From the -Omics Perspective: Lessons Learnt.Annals of neurology · 2026Review
- The Progress of Active Immunotherapy for Parkinson's Disease.International journal of molecular sciences · 2026Review
- Toward precision neuroscience in Alzheimer's disease: the role of multimodal AI.Frontiers in aging neuroscience · 2026Review
- Astrocytic KFrontiers in aging neuroscience · 2026Review
- Shared Neuroinflammatory Mechanisms Across Dementia Types: An Integrative Review.International journal of molecular sciences · 2025Review
- Proteomics research in aging: a bibliometric and visualized analysis of evolution and emerging trends (1998-2024 and early 2025).Biogerontology · 2025Article
- The silent saboteur: oxidative stress and the path to cognitive dysfunction.Neurodegenerative disease management · 2025Review
- Interaction of metabolic and inflammatory dysregulation on central degeneration and cognitive function in behavioral variant Frontotemporal dementia.Journal of neurology · 2025Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Neurodegenerative disorders such as Alzheimer's disease (AD), Lewy body diseases (LBD), and the amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) spectrum are defined by the accumulation of specific misfolded protein aggregates. However, the mechanisms by which each proteinopathy leads to neurodegeneration remain elusive. We hypothesized that there is a common "pan-neurodegenerative" gene expression signature driving pathophysiology across these clinically and pathologically diverse proteinopathies. To test this hypothesis, we performed a systematic review of human CNS transcriptomics datasets from AD, LBD, and ALS-FTD patients and age-matched controls in the Gene Expression Omnibus (GEO) and ArrayExpress databases, followed by consistent processing of each dataset, meta-analysis, pathway enrichment, and overlap analyses. After applying pre-specified eligibility criteria and stringent data pre-processing, a total of 2600 samples from 26 AD, 21 LBD, and 13 ALS-FTD datasets were included in the meta-analysis. The pan-neurodegenerative gene signature is characterized by an upregulation of innate immunity, cytoskeleton, and transcription and RNA processing genes, and a downregulation of the mitochondrial electron transport chain. Pathway enrichment analyses also revealed the upregulation of neuroinflammation (including Toll-like receptor, TNF, and NFκB signaling) and phagocytosis, and the downregulation of mitochondrial oxidative phosphorylation, lysosomal acidification, and ubiquitin-proteasome pathways. Our findings suggest that neuroinflammation and a failure in both neuronal energy metabolism and protein degradation systems are consistent features underlying neurodegenerative diseases, despite differences in the extent of neuronal loss and brain regions involved.
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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 Socratic graph.