ArticleNature aging2024
Serum proteomics reveal APOE-ε4-dependent and APOE-ε4-independent protein signatures in Alzheimer's disease.
Article in Nature aging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers, 1 of them a synthesis that pooled it.
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
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The role of APOE ε4 in modulating the relationship between non-genetic risk factors and dementia: a system review and meta-analysis.Journal of neurology · 2025Pooled it
- A modifiable driver of dementia: cognitive impairment in primary aldosteronism.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- EPIC4ND-European Prospective Investigation into Cancer and Nutrition follow-up for neurodegenerative diseases.European journal of epidemiology · 2026Article
- Long-term temporal stability of circulating proteins in older adults.Nature communications · 2026Article
- Proteomic signatures of the APOE ε4 and APOE ε2 genetic variants and Alzheimer's disease.Nature aging · 2026Article
- Plasma proteomics ofmedRxiv : the preprint server for health sciences · 2026Article
- APOE-stratified Proteomic and Metabolomic Analysis Reveals Mitochondrial Dysfunction Inflammation and Lipid Dysregulation in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Human CSF proteogenomics links genetic variation to neurodegenerative disease proteins.medRxiv : the preprint server for health sciences · 2026Article
- Plasma Proteomic Analysis ofmedRxiv : the preprint server for health sciences · 2026Article
- Amyloid-Frontiers in aging neuroscience · 2026Article
- Proteomic Insight Into Alzheimer's Disease Pathogenesis Pathways.Proteomics · 2025Review
- Long-term temporal stability of circulating proteins in older adults.bioRxiv : the preprint server for biology · 2025Article
- Association Between Plasma Metabolomic Profile and Machine Learning-Based Brain Age.Aging cell · 2025Article
- Plasma proteomic associations with Alzheimer's disease endophenotypes.Nature aging · 2025Article
- Cerebrospinal fluid proteomic signatures in cognitively normal individuals identify distinct clusters linked to neurodegeneration.Nature aging · 2025Article
- APOE ε4 carriers share immune-related proteomic changes across neurodegenerative diseases.Nature medicine · 2025Article
- The Global Neurodegeneration Proteomics Consortium: biomarker and drug target discovery for common neurodegenerative diseases and aging.Nature medicine · 2025Article
- Interrogating the plasma proteome of repetitive head impact exposure and chronic traumatic encephalopathy.Molecular neurodegeneration · 2025Article
- Large-scale plasma proteomic profiling unveils diagnostic biomarkers and pathways for Alzheimer's disease.Nature aging · 2025Article
Corrections and comments
- Erratum issued
- Update of
- Update of
Authors and funding
27 authors.
Funding
Abstract
A deeper understanding of the molecular processes underlying late-onset Alzheimer's disease (LOAD) could aid in biomarker and drug target discovery. Using high-throughput serum proteomics in the prospective population-based Age, Gene/Environment Susceptibility-Reykjavik Study (AGES) cohort of 5,127 older Icelandic adults (mean age, 76.6 ± 5.6 years), we identified 303 proteins associated with incident LOAD over a median follow-up of 12.8 years. Over 40% of these proteins were associated with LOAD independently of APOE-ε4 carrier status, were implicated in neuronal processes and overlapped with LOAD protein signatures in brain and cerebrospinal fluid. We identified 17 proteins whose associations with LOAD were strongly dependent on APOE-ε4 carrier status, with mostly consistent associations in cerebrospinal fluid. Remarkably, four of these proteins (TBCA, ARL2, S100A13 and IRF6) were downregulated by APOE-ε4 yet upregulated due to LOAD, a finding replicated in external cohorts and possibly reflecting a response to disease onset. These findings highlight dysregulated pathways at the preclinical stages of LOAD, including those both independent of and dependent on APOE-ε4 status.
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.