Evidence map›Paper›PMID 32998767›Full record

ArticleAlzheimer's research & therapy2020

Immunomodulatory sphingosine-1-phosphates as plasma biomarkers of Alzheimer's disease and vascular cognitive impairment.

Xin Ying Chua, Yuek Ling Chai, Wee Siong Chew, Joyce R Chong, Hui Li Ang, Ping Xiang, Kaddy Camara, Amy R Howell, Federico Torta, Markus R Wenk and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 13% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. Structural insights into the G-protein subtype selectivity revealed by human sphingosine-1-phosphate receptor 3-GProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Gut microbiota mediates semaglutide attenuation of diabetes-associated cognitive decline.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article
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

15 authors at 3 institutions in 2 countries.

Xin Ying ChuaDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, 117597, Singapore.
Yuek Ling ChaiDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, 117597, Singapore.
Wee Siong ChewDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, 117597, Singapore.
Joyce R ChongDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, 117597, Singapore.
Hui Li AngDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, 117597, Singapore.
Ping XiangDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, 117597, Singapore.
Kaddy CamaraDepartment of Chemistry, University of Connecticut, Storrs, CT, USA.
Amy R HowellDepartment of Chemistry, University of Connecticut, Storrs, CT, USA.
Federico TortaSingapore Lipidomics Incubator (SLING), Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
Markus R WenkSingapore Lipidomics Incubator (SLING), Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
Saima HilalDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, 117597, Singapore.
Narayanaswamy VenketasubramanianRaffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore.
Christopher P ChenDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, 117597, Singapore.
Deron R HerrDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, 117597, Singapore. phcdrh@nus.edu.sg.
Mitchell K P LaiDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, 117597, Singapore. mitchell.lai@dementia-research.org.ORCID 0000-0001-7685-1424
National University of Singapore · SGUniversity of Connecticut · USRaffles Institution · SG

Funding

Harnessing NKT Cell Activation by GlycolipidsR01GM111849 · NIGMS · UNIVERSITY OF CONNECTICUT STORRS · PI HOWELL, AMY · 2019 to 2022
$2.1M
Harnessing NKT Cell Activation by GlycolipidsU01GM111849 · NIGMS · UNIVERSITY OF CONNECTICUT STORRS · PI HOWELL, AMY · 2014 to 2017
$1.9M
NIGMS NIH HHS GM111849NIGMS NIH HHS R01 GM111849NIGMS NIH HHS U01 GM111849
6 · The paper itself

Abstract

backgroundThere has been ongoing research impetus to uncover novel blood-based diagnostic and prognostic biomarkers for Alzheimer's disease (AD), vascular dementia (VaD), and related cerebrovascular disease (CEVD)-associated conditions within the spectrum of vascular cognitive impairment (VCI). Sphingosine-1-phosphates (S1Ps) are signaling lipids which act on the S1PR family of cognate G-protein-coupled receptors and have been shown to modulate neuroinflammation, a process known to be involved in both neurodegenerative and cerebrovascular diseases. However, the status of peripheral S1P in AD and VCI is at present unclear.

methodsWe obtained baseline bloods from individuals recruited into an ongoing longitudinal cohort study who had normal cognition (N = 80); cognitive impairment, no dementia (N = 160); AD (N = 113); or VaD (N = 31), along with neuroimaging assessments of cerebrovascular diseases. Plasma samples were processed for the measurements of major S1P species: d16:1, d17:1, d18:0, and d18:1, along with pro-inflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF). Furthermore, in vitro effects of S1Ps on cytokine expression were also studied in an astrocytoma cell line and in rodent primary astrocytes.

resultsOf the S1Ps species measured, only d16:1 S1P was significantly reduced in the plasma of VaD, but not AD, patients, while the d18:1 to d16:1 ratios were increased in all cognitive subgroups (CIND, AD, and VaD). Furthermore, d18:1 to d16:1 ratios correlated with levels of IL-6, IL-8, and TNF. In both primary astrocytes and an astroglial cell line, treatment with d16:1 or d18:1 S1P resulted in the upregulation of mRNA transcripts of pro-inflammatory cytokines, with d18:1 showing a stronger effect than d16:1. Interestingly, co-treatment assays showed that the addition of d16:1 reduced the extent of d18:1-mediated gene expression, indicating that d16:1 may function to "fine-tune" the pro-inflammatory effects of d18:1.

conclusionTaken together, our data suggest that plasma d16:1 S1P may be useful as a diagnostic marker for VCI, while the d18:1 to d16:1 S1P ratio is an index of dysregulated S1P-mediated immunomodulation leading to chronic inflammation-associated neurodegeneration and cerebrovascular damage.

Indexed as

Alzheimer DiseaseCognitive DysfunctionBiomarkersHumansImmunomodulationLongitudinal StudiesPhosphatesSphingosineBiomarkersPhosphatesSphingosineAlzheimer’s diseaseBiomarkersImmunomodulationNeuroinflammationSphingosine-1-phosphateVascular cognitive impairment

Identifiers

PMID32998767
PMCPMC7528375
OpenAlexW3091283841

What Socratic 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 Socratic graph.