Evidence map›Paper›PMID 27358067›Full record

Trial reportAlzheimer's research & therapy2016

The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease.

Hussein N Yassine, Varun Rawat, Wendy J Mack, Joseph F Quinn, Karin Yurko-Mauro, Eileen Bailey-Hall, Paul S Aisen, Helena C Chui, Lon S Schneider

Registry-linked trialOpen access · goldAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00440050 (A Randomized Double-Blind Placebo-Controlled Trial Of The Effects Of Docosahexaenoic Acid), which is not on this map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
8.2field-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.

NCT00440050 phase3completednot on this map

A Randomized Double-Blind Placebo-Controlled Trial Of The Effects Of Docosahexaenoic Acid (DHA) In Slowing The Progression Of Alzheimer's Disease

TypeinterventionalSponsorAlzheimer's Disease Cooperative Study (ADCS)Ran2007 to 2009Enrolled402ConditionsAlzheimer's DiseaseArmsDHA (Docosahexaenoic Acid), Placebo
3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Trial
  6. Review
  7. Review
  8. Development of potent, selective cPLAnpj drug discovery · 2026
    Article
  9. Article
  10. Concentrations of the serum long-chain omega-3 polyunsaturated fatty acids and hair mercury in men in different apolipoprotein E phenotypes.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025
    Article
  11. Nutrition: A non-negligible factor in the pathogenesis and treatment of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  12. The Influence ofNutrients · 2023
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Radiosynthesis of 20-[Prostaglandins, leukotrienes, and essential fatty acids · 2022
    Article
  18. Article
  19. Calcium-dependent cytosolic phospholipase AMolecular neurodegeneration · 2022
    Article
  20. Review
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

9 authors at 2 institutions in 1 country.

Hussein N YassineDepartment of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. hyassine@usc.edu.
Varun RawatDepartment of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Wendy J MackDepartment of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Joseph F QuinnDepartment of Neurology, Oregon Health & Science University, and Portland VA Medical Center , Portland, OR, USA.
Karin Yurko-MauroClinical Research Department, DSM Nutritional Products, Columbia, MD, USA.
Eileen Bailey-HallClinical Research Department, DSM Nutritional Products, Columbia, MD, USA.
Paul S AisenAlzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Helena C ChuiDepartment of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Lon S SchneiderDepartment of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
University of Southern California · USOregon Health & Science University · US

Funding

TRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2M
VASCULAR RISK AND COGNITIVE STATUS IN A LATINO POPULATIONP50AG005142 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TOGA, ARTHUR W · 1985 to 2019
$41.0M
The Effect of Saturated Fat Ingestion on the HDL ProteomeK23HL107389 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI YASSINE, HUSSEIN N · 2012 to 2016
$648k
NHLBI NIH HHS K23 HL107389NIA NIH HHS P50 AG005142NIA NIH HHS U01 AG010483
6 · The paper itself

Abstract

backgroundApolipoprotein E (APOE) ɛ4 and low cerebrospinal fluid (CSF) amyloid-β42 (Aβ42) levels are predictors for developing Alzheimer's disease (AD). The results of several studies indicate an interaction between docosahexaenoic acid (DHA) consumption and cognitive outcomes by APOE genotype. Our objective in the present study was to examine whether APOE ɛ4 genotype and low CSF Aβ42 levels were associated with reduced delivery of DHA to CSF in the Alzheimer's Disease Cooperative Study-sponsored DHA clinical trial.

methodsPhospholipid DHA was assayed in the plasma of 384 participants and CSF of 70 participants at baseline. Forty-four of the 70 participants completed the 18-month follow-up visit after allocation to placebo (n = 15) or DHA (n = 29). Plasma and CSF DHA levels, CSF Aβ42, Tau, and phosphorylated Tau were measured at baseline and after the 18-month intervention. Participants were divided into tertiles based on baseline Aβ42 CSF levels. To assess DHA delivery across the blood-brain barrier, the ratio of CSF to plasma DHA levels was calculated.

resultsAt baseline, there were no significant differences between CSF or plasma phospholipid DHA levels by CSF Aβ42 tertiles or ɛ4 status. After 18 months of DHA supplementation, participants at the lowest Aβ42 tertile had significantly lower CSF DHA levels (p = 0.01) and lower CSF-to-plasma DHA ratios (p = 0.05) compared to the other tertiles. Baseline CSF Aβ42 levels were significantly lower in ɛ4 carriers than in ɛ4 noncarriers (p = 0.01). Participants carrying the ɛ4 allele (n = 25) demonstrated a less pronounced increase in CSF DHA level compared with noncarriers (n = 4), with a possible interaction effect between treatment and APOE genotype (p = 0.07).

conclusionsAPOE ɛ4 allele and lower CSF Aβ42 levels were associated with less transport of DHA to CSF. Brain amyloid pathology may limit the delivery of DHA to the brain in AD.

trial registrationClinicaltrials.gov identifier: NCT00440050 . Registered on 22 Feb 2007.

Indexed as

Dietary SupplementsAlzheimer DiseaseAmyloid beta-PeptidesApolipoprotein E4BiomarkersDocosahexaenoic AcidsDouble-Blind MethodFollow-Up StudiesGenotypeHumansPeptide FragmentsPhosphorylationtau ProteinsAmyloid beta-Peptidesamyloid beta-protein (1-42)Apolipoprotein E4BiomarkersDocosahexaenoic AcidsMAPT protein, humanPeptide Fragmentstau ProteinsAlzheimer’s diseaseAmyloidAPOECerebrospinal fluid

Identifiers

PMID27358067
PMCPMC4928349
OpenAlexW2464293682

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.