ArticleMolecular psychiatry2021
Integrative brain transcriptome analysis links complement component 4 and HSPA2 to the APOE ε2 protective effect in Alzheimer disease.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 3 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
38 citing papers in PubMed, 3 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.Genome biology · 2025Pooled it
- Pooled it
- Systematic review and meta-analysis of bulk RNAseq studies in human Alzheimer's disease brain tissue.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Cell-based polygenic risk scores predict clinical progression and prioritize network-based therapeutic targets in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Neuid: A Novel Neuron-Enriched LncRNA that Connects Epigenetic Gene Silencing to Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Blood-Brain Network-Based Polygenic Risk Scores Reveal Biomarker Signatures and the Progression of Alzheimer's Disease.Journal of clinical medicine · 2026Article
- Immune involvement in neuropsychiatric disorders: Insights from single-cell transcriptomic studies.Psychiatry and clinical neurosciences · 2026Review
- Proteomic profiling of olfactory exfoliates from people with subjective cognitive complaints reveal networks of olfactory biomarkers of cognitive performance.Frontiers in aging neuroscience · 2026Article
- A spatially informed matrix normal model for gene co-expression analysis in spatial transcriptomics studies.Nucleic acids research · 2025Article
- Alzheimer's disease multi-ancestry genome-wide interaction and stratified study with smoking.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Perinatal Choline Supplementation Promotes Resilience Against Progression of Alzheimer's Disease-Like Brain Transcriptomic Signatures in AppAging cell · 2025Article
- Novel differentially expressed genes and multiple biological pathways for Alzheimer's disease identified in brain tissue from African American donors.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Genome-wide pleiotropy analysis of longitudinal blood pressure and harmonized cognitive performance measures.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Emerging Role of Oligodendrocytes Malfunction in the Progression of Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Review
- Global C3 lowering in adulthood protects against hippocampal dysfunction and cognitive impairment in aged mice.Research square · 2025Article
- Analysis of human brain RNA-seq data reveals combined effects of 4 types of RNA modifications and 18 types of programmed cell death on Alzheimer's disease.Journal of translational medicine · 2025Article
- Multiomics from Alzheimer's Brains and Mesenchymal Stem Cell-Derived Extracellular Vesicles Identifies Therapeutic Potential of Specific Subpopulations to Target Mitochondrial Proteostasis.Journal of central nervous system disease · 2025Article
- Prognostic Value of Apolipoprotein E in Predicting One-year Mortality in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2025Article
- Systematic review and meta-analysis of bulk RNAseq studies in human Alzheimer's disease brain tissue.bioRxiv : the preprint server for biology · 2024Article
- Integrative Multi-omics Analysis to Characterize Herpes Virus Infection Increases the Risk of Alzheimer's Disease.Molecular neurobiology · 2024Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Mechanisms underlying the protective effect of apolipoprotein E (APOE) ε2 against Alzheimer disease (AD) are not well understood. We analyzed gene expression data derived from autopsied brains donated by 982 individuals including 135 APOE ɛ2/ɛ3 carriers. Complement pathway genes C4A and C4B were among the most significantly differentially expressed genes between ɛ2/ɛ3 AD cases and controls. We also identified an APOE ε2/ε3 AD-specific co-expression network enriched for astrocytes, oligodendrocytes and oligodendrocyte progenitor cells containing the genes C4A, C4B, and HSPA2. These genes were significantly associated with the ratio of phosphorylated tau at position 231 to total Tau but not with amyloid-β 42 level, suggesting this APOE ɛ2 related co-expression network may primarily be involved with tau pathology. HSPA2 expression was oligodendrocyte-specific and significantly associated with C4B protein. Our findings provide the first evidence of a crucial role of the complement pathway in the protective effect of APOE ε2 for AD.
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Registered trials
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