Evidence map›Paper›PMID 26617567›Full record

ArticleFrontiers in neurology2015

Plasma 24-metabolite Panel Predicts Preclinical Transition to Clinical Stages of Alzheimer's Disease.

Massimo S Fiandaca, Xiaogang Zhong, Amrita K Cheema, Michael H Orquiza, Swathi Chidambaram, Ming T Tan, Carole Roan Gresenz, Kevin T FitzGerald, Mike A Nalls, Andrew B Singleton and 2 more

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In one paragraph

Article in Frontiers in neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

69 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
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  7. Sex-specific associations between AD genotype and the microbiome of human amyloid beta knock-in (hAβ-KI) mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  8. Article
  9. Article
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  11. Cardiovascular Disease and Alzheimer's Disease: The Heart-Brain Axis.Journal of the American Heart Association · 2023
    Review
  12. Article
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  16. Article
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  19. A metabolite panel that differentiates Alzheimer's disease from other dementia types.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022
    Article
  20. Review

9 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

12 authors.

Massimo S FiandacaDepartment of Neurology, University of California Irvine , Irvine, CA , USA ; Department of Neurological Surgery, University of California Irvine , Irvine, CA , USA.
Xiaogang ZhongDepartment of Bioinformatics, Biostatistics and Biomathematics, Georgetown University Medical Center , Washington, DC , USA.
Amrita K CheemaDepartments of Oncology and Biochemistry, Georgetown University Medical Center , Washington, DC , USA.
Michael H OrquizaDepartment of Neuroscience, Georgetown University Medical Center , Washington, DC , USA.
Swathi ChidambaramSchool of Medicine, Georgetown University Medical Center , Washington, DC , USA.
Ming T TanDepartment of Bioinformatics, Biostatistics and Biomathematics, Georgetown University Medical Center , Washington, DC , USA.
Carole Roan GresenzDepartment of Economics, Sociology and Statistics, RAND Corporation , Arlington, VA , USA.
Kevin T FitzGeraldPellegrino Center for Clinical Bioethics, Georgetown University Medical Center , Washington, DC , USA.
Mike A NallsLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD , USA.
Andrew B SingletonLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD , USA.
Mark MapstoneDepartment of Neurology, University of California Irvine , Irvine, CA , USA.
Howard J FederoffDepartment of Neurology, University of California Irvine , Irvine, CA , USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We recently documented plasma lipid dysregulation in preclinical late-onset Alzheimer's disease (LOAD). A 10 plasma lipid panel, predicted phenoconversion and provided 90% sensitivity and 85% specificity in differentiating an at-risk group from those that would remain cognitively intact. Despite these encouraging results, low positive predictive values limit the clinical usefulness of this panel as a screening tool in subjects aged 70-80 years or younger. In this report, we re-examine our metabolomic data, analyzing baseline plasma specimens from our group of phenoconverters (n = 28) and a matched set of cognitively normal subjects (n = 73), and discover and internally validate a panel of 24 plasma metabolites. The new panel provides a classifier with receiver operating characteristic area under the curve for the discovery and internal validation cohort of 1.0 and 0.995 (95% confidence intervals of 1.0-1.0, and 0.981-1.0), respectively. Twenty-two of the 24 metabolites were significantly dysregulated lipids. While positive and negative predictive values were improved compared to our 10-lipid panel, low positive predictive values provide a reality check on the utility of such biomarkers in this age group (or younger). Through inclusion of additional significantly dysregulated analyte species, our new biomarker panel provides greater accuracy in our cohort but remains limited by predictive power. Unfortunately, the novel metabolite panel alone may not provide improvement in counseling and management of at-risk individuals but may further improve selection of subjects for LOAD secondary prevention trials. We expect that external validation will remain challenging due to our stringent study design, especially compared with more diverse subject cohorts. We do anticipate, however, external validation of reduced plasma lipid species as a predictor of phenoconversion to either prodromal or manifest LOAD.

Indexed as

Alzheimer’s diseasebiomarkerseconomicsethicslipidsmetabolomicsrisk assessment

Identifiers

PMID26617567
PMCPMC4642213

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Registered trials

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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.