ArticleNature medicine2025
APOE ε4 carriers share immune-related proteomic changes across neurodegenerative diseases.
Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed.
- Proteomic signatures of protected APOE ε4 carriers reveal causal pathways associated with delayed Alzheimer's disease onset.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- APOE4 disrupts the central dogma by arresting neuronal proteome dynamics.bioRxiv : the preprint server for biology · 2026Article
- Protective mutations associated with APOE in Alzheimer's disease.Molecular psychiatry · 2026Review
- Investigating the Causal Links between the Aging Process and Alzheimer's Disease Pathogenesis.International journal of stem cells · 2026Review
- Review
- APOE ε4 influences the widespread TDP-43 pathological subtype in sporadic amyotrophic lateral sclerosis.Acta neuropathologica · 2026Article
- Review
- Proteomic Signatures of ProtectedmedRxiv : the preprint server for health sciences · 2026Article
- Proteomic signatures of the APOE ε4 and APOE ε2 genetic variants and Alzheimer's disease.Nature aging · 2026Article
- How does type 2 diabetes modify the risk of Alzheimer's disease?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- The emerging role of CETP inhibition in the prevention of Alzheimer's disease.American journal of preventive cardiology · 2026Review
- A critical appraisal of the link between apolipoprotein E and Tau.Current opinion in neurology · 2026Review
- Cross-trait genomic and sequential analyses of multiple omics datasets identified shared genetic components for the gut-eye axis.Human genomics · 2026Article
- Divergent Biological Consequences of APOE Isoforms Across Industrialized and Non-Industrial Environments.bioRxiv : the preprint server for biology · 2026Article
- Alzheimer's Disease as a Disorder of Neuroimmune Dysregulation.Neurology international · 2026Review
- Sex and APOE genotype specific brain regional vulnerability to Alzheimer's Disease.GeroScience · 2026Article
- Genomics link obesity and type 2 diabetes to Alzheimer's disease to unveil novel biological insights.medRxiv : the preprint server for health sciences · 2026Article
- Plasma Proteomic Analysis ofmedRxiv : the preprint server for health sciences · 2026Article
- Circulating inflammatory proteins predict dementia risk, and are linked to structural brain changes and modifiable risk factors.Alzheimer's research & therapy · 2026Article
- Chronic Reactivation of Persistent Human Herpesviruses EBV, HHV-6 and VZV and Heightened Anti-dUTPase IgG Antibodies Are a Recurrent Hallmark in Post-Infectious ME/CFS and is Associated With Fatigue.Journal of medical virology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
The APOE ε4 genetic variant is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) and is increasingly being implicated in other neurodegenerative diseases. Using the Global Neurodegeneration Proteomics Consortium SomaScan dataset covering 1,346 cerebrospinal fluid (CSF) and 9,924 plasma samples, we used machine learning-based proteome profiling to identify an APOE ε4 proteomic signature shared across individuals with AD, frontotemporal dementia (FTD), Parkinson's disease dementia (PDD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and nonimpaired controls. This signature was enriched in pro-inflammatory immune and infection pathways as well as immune cells, including monocytes, T cells and natural killer cells. Analysis of the dorsolateral prefrontal cortex proteome for 262 donors from the Accelerating Medicines Partnership for AD UPenn Proteomics Study revealed a consistent APOE ε4 phenotype, independent of neurodegenerative pathology, including amyloid-β tau and gliosis for all diseases, as well as TDP-43 in ALS and FTD cases, and α-synuclein in PD and PDD cases. While systemic proteomic changes were consistent across APOE ε4 carriers, their relationship with clinical and lifestyle factors, such as hypertension and smoking, varied by disease. These findings suggest APOE ε4 confers a systemic biological vulnerability that is necessary but not sufficient for neurodegeneration, emphasizing the need to consider gene-environment interactions. Overall, our study reveals a conserved APOE ε4-associated pro-inflammatory immune signature persistent across the brain, CSF and plasma irrespective of neurodegenerative disease, highlighting a fundamental, disease-independent biological vulnerability to neurodegeneration. This work reframes APOE ε4 as a pleiotropic immune modulator rather than an AD-specific risk gene, providing a foundation for precision biomarker development and early intervention strategies across neurodegenerative diseases.
Indexed as
Identifiers
What Socratic holds
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.