SynthesisPLoS genetics2014
Genome-wide association study of CSF levels of 59 alzheimer's disease candidate proteins: significant associations with proteins involved in amyloid processing and inflammation.
Synthesis in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 7 of them syntheses 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
84 citing papers in PubMed, 7 syntheses or guidelines pooled it, 129 citations in OpenAlex.
- A systematic review and meta-analysis of metalloproteinases in patients with Alzheimer's disease and mild cognitive impairment.Journal of Alzheimer's disease : JAD · 2026Pooled it
- Genetic Variability in Molecular Pathways Implicated in Alzheimer's Disease: A Comprehensive Review.Frontiers in aging neuroscience · 2021Pooled it
- Detecting fitness epistasis in recently admixed populations with genome-wide data.BMC genomics · 2020Pooled it
- Genome-wide study of immune biomarkers in cerebrospinal fluid and serum from patients with bipolar disorder and controls.Translational psychiatry · 2020Pooled it
- Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.Nature genetics · 2019Pooled it
- A Common Variant of IL-6R is Associated with Elevated IL-6 Pathway Activity in Alzheimer's Disease Brains.Journal of Alzheimer's disease : JAD · 2017Pooled it
- Renin-angiotensin system gene expression and neurodegenerative diseases.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2016Pooled it
- Human CSF proteogenomics links genetic variation to neurodegenerative disease proteins.medRxiv : the preprint server for health sciences · 2026Article
- CSF proteomic quantitative trait loci mapping reveals genetic insights into Alzheimer's disease.Molecular neurodegeneration advances · 2026Article
- DDT exposure induces microglial activation and disease-associated microglial signatures: Relevance to mechanisms of Alzheimer's disease.Neurotoxicology · 2025Article
- Identification of Druggable Targets for Alzheimer's Disease by Analyzing Circulating Inflammatory Proteins With Mendelian Randomization.Brain and behavior · 2025Article
- Uncovering Proteins Commonly Expressed Between Heart Failure and Dementia Using Bioinformatic Tools.Current issues in molecular biology · 2025Article
- Associations among Angiotensin-Converting Enzyme, Neuroinflammation, and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease in Non-Dementia Adults.Neurotoxicity research · 2025Article
- The Contribution of the Renin-Angiotensin System to Alzheimer's Disease.Current topics in behavioral neurosciences · 2025Review
- Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer's disease.Nature genetics · 2024Article
- Connecting dementia risk loci to the CSF proteome identifies pathophysiological leads for dementia.Brain : a journal of neurology · 2024Article
- SDS3 regulates microglial inflammation by modulating the expression of the upstream kinase ASK1 in the p38 MAPK signaling pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Promises and Challenges of populational Proteomics in Health and Disease.Molecular & cellular proteomics : MCP · 2024Article
- The Role of Atypical Chemokine Receptors in Neuroinflammation and Neurodegenerative Disorders.International journal of molecular sciences · 2023Review
- Charting the Next Road Map for CSF Biomarkers in Alzheimer's Disease and Related Dementias.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
24 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
19 authors at 3 institutions in 1 country.
Funding
Abstract
Cerebrospinal fluid (CSF) 42 amino acid species of amyloid beta (Aβ42) and tau levels are strongly correlated with the presence of Alzheimer's disease (AD) neuropathology including amyloid plaques and neurodegeneration and have been successfully used as endophenotypes for genetic studies of AD. Additional CSF analytes may also serve as useful endophenotypes that capture other aspects of AD pathophysiology. Here we have conducted a genome-wide association study of CSF levels of 59 AD-related analytes. All analytes were measured using the Rules Based Medicine Human DiscoveryMAP Panel, which includes analytes relevant to several disease-related processes. Data from two independently collected and measured datasets, the Knight Alzheimer's Disease Research Center (ADRC) and Alzheimer's Disease Neuroimaging Initiative (ADNI), were analyzed separately, and combined results were obtained using meta-analysis. We identified genetic associations with CSF levels of 5 proteins (Angiotensin-converting enzyme (ACE), Chemokine (C-C motif) ligand 2 (CCL2), Chemokine (C-C motif) ligand 4 (CCL4), Interleukin 6 receptor (IL6R) and Matrix metalloproteinase-3 (MMP3)) with study-wide significant p-values (p<1.46×10-10) and significant, consistent evidence for association in both the Knight ADRC and the ADNI samples. These proteins are involved in amyloid processing and pro-inflammatory signaling. SNPs associated with ACE, IL6R and MMP3 protein levels are located within the coding regions of the corresponding structural gene. The SNPs associated with CSF levels of CCL4 and CCL2 are located in known chemokine binding proteins. The genetic associations reported here are novel and suggest mechanisms for genetic control of CSF and plasma levels of these disease-related proteins. Significant SNPs in ACE and MMP3 also showed association with AD risk. Our findings suggest that these proteins/pathways may be valuable therapeutic targets for AD. Robust associations in cognitively normal individuals suggest that these SNPs also influence regulation of these proteins more generally and may therefore be relevant to other diseases.
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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.