Evidence map›Paper›PMID 26202100›Full record

SynthesisScientific reports2015

Integrated genomic approaches identify major pathways and upstream regulators in late onset Alzheimer's disease.

Xinzhong Li, Jintao Long, Taigang He, Robert Belshaw, James Scott

Open access · goldAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 6 pooled it
7.2field-weighted citation impact, top 2% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 6 syntheses or guidelines pooled it, 145 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. A Meta-Analysis of Alzheimer's Disease Brain Transcriptomic Data.Journal of Alzheimer's disease : JAD · 2019
    Pooled it
  6. Pooled it
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Plasma and CSF biomarkers of aging and cognitive decline in Caribbean vervets.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  17. Article
  18. Article
  19. Review
  20. Review

28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Xinzhong LiCentre for Biostatistics, Bioinformatics and Biomarkers, Plymouth University, Plymouth UK.
Jintao LongCentre for Biostatistics, Bioinformatics and Biomarkers, Plymouth University, Plymouth UK.
Taigang HeInstitute of Cardiovascular and Cell Sciences, St. George University, London UK.
Robert BelshawSchool of Biomedicine and Healthcare Sciences, Plymouth University, Plymouth UK.
James ScottNational Heart and Lung Institute, Imperial College, London UK.
University of Plymouth · GBImperial College London · GBSt George's, University of London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Previous studies have evaluated gene expression in Alzheimer's disease (AD) brains to identify mechanistic processes, but have been limited by the size of the datasets studied. Here we have implemented a novel meta-analysis approach to identify differentially expressed genes (DEGs) in published datasets comprising 450 late onset AD (LOAD) brains and 212 controls. We found 3124 DEGs, many of which were highly correlated with Braak stage and cerebral atrophy. Pathway Analysis revealed the most perturbed pathways to be (a) nitric oxide and reactive oxygen species in macrophages (NOROS), (b) NFkB and (c) mitochondrial dysfunction. NOROS was also up-regulated, and mitochondrial dysfunction down-regulated, in healthy ageing subjects. Upstream regulator analysis predicted the TLR4 ligands, STAT3 and NFKBIA, for activated pathways and RICTOR for mitochondrial genes. Protein-protein interaction network analysis emphasised the role of NFKB; identified a key interaction of CLU with complement; and linked TYROBP, TREM2 and DOK3 to modulation of LPS signalling through TLR4 and to phosphatidylinositol metabolism. We suggest that NEUROD6, ZCCHC17, PPEF1 and MANBAL are potentially implicated in LOAD, with predicted links to calcium signalling and protein mannosylation. Our study demonstrates a highly injurious combination of TLR4-mediated NFKB signalling, NOROS inflammatory pathway activation, and mitochondrial dysfunction in LOAD.

Indexed as

Calcium SignalingAlzheimer DiseaseBrainGene Expression ProfilingGene Expression RegulationGenomicsHumansNerve Tissue ProteinsProtein Interaction MappingProteomeSystems IntegrationNerve Tissue ProteinsProteome

Identifiers

PMID26202100
PMCPMC4511863
OpenAlexW2276757459

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.