Trial reportJournal of Alzheimer's disease : JAD2020
Effect of APOE Genotype on Plasma Docosahexaenoic Acid (DHA), Eicosapentaenoic Acid, Arachidonic Acid, and Hippocampal Volume in the Alzheimer's Disease Cooperative Study-Sponsored DHA Clinical Trial.
Trial report in Journal of Alzheimer's disease : JAD, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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
32 citing papers in PubMed, 71 citations in OpenAlex.
- ω-3 PUFA for Secondary Prevention of White Matter Lesions and Neuronal Integrity Breakdown in Older Adults: A Randomized Clinical Trial.JAMA network open · 2024Trial
- Long-term major histocompatibility complex class I suppression in astronauts and clinical implications.Communications biology · 2026Review
- Omega-3 Fatty Acids and Alzheimer's Disease: Toward a New Understanding of Neuroprotective Mechanisms and Intervention Strategies.Marine drugs · 2026Review
- Polygenic predisposition modifies the associations of fish oil supplementation with circulating omega-3 fatty acids: a cross-sectional gene-diet interaction study in UK Biobank.medRxiv : the preprint server for health sciences · 2026Article
- Scientific Opinion on the tolerable upper intake level for supplemental docosahexaenoic acid.EFSA journal. European Food Safety Authority · 2026Article
- Development of potent, selective cPLAnpj drug discovery · 2026Article
- A multi-level gene-diet interaction analysis of fish oil and 14 polyunsaturated fatty acid traits identifies the FADS and GPR12 loci.HGG advances · 2025Article
- Article
- Nutrition: A non-negligible factor in the pathogenesis and treatment of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- APOEε4 alters ApoE and Fabp7 in frontal cortex white matter in prodromal Alzheimer's disease.Journal of neuroinflammation · 2025Article
- Arachidonic Acid Mobilization and Peroxidation Promote Microglial Dysfunction in Aβ Pathology.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Apolipoprotein E potently inhibits ferroptosis by blocking ferritinophagy.Molecular psychiatry · 2024Article
- High-Fat Diets in Animal Models of Alzheimer's Disease: How Can Eating Too Much Fat Increase Alzheimer's Disease Risk?Journal of Alzheimer's disease : JAD · 2024Review
- Synthesis and Preclinical Evaluation of 22-[ACS chemical neuroscience · 2023Article
- Impact of Nutritional Interventions on Alzheimer's Disease: A Systematic Review and Meta-Analysis.Cureus · 2023Review
- Amelioration of Cognitive and Olfactory System Deficits in APOE4 Transgenic Mice with DHA Treatment.Molecular neurobiology · 2023Article
- Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- Midlife omega-3 fatty acid intake predicts later life white matter microstructure in an age- and APOE-dependent manner.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- ApoE in Alzheimer's disease: pathophysiology and therapeutic strategies.Molecular neurodegeneration · 2022Review
- Radiosynthesis of 20-[Prostaglandins, leukotrienes, and essential fatty acids · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDocosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) play key roles in several metabolic processes relevant to Alzheimer's disease (AD) pathogenesis and neuroinflammation. Carrying the APOEɛ4 allele (APOE4) accelerates omega-3 polyunsaturated fatty acid (PUFA) oxidation. In a pre-planned subgroup analysis of the Alzheimer's Disease Cooperative Study-sponsored DHA clinical trial, APOE4 carriers with mild probable AD had no improvements in cognitive outcomes compared to placebo, while APOE 4 non-carriers showed a benefit from DHA supplementation.
objectiveWe sought to clarify the effect of APOEɛ4/ɛ4 on both the ratio of plasma DHA and EPA to AA, and on hippocampal volumes after DHA supplementation.
methodsPlasma fatty acids and APOE genotype were obtained in 275 participants randomized to 18 months of DHA supplementation or placebo. A subset of these participants completed brain MRI imaging (n = 86) and lumbar punctures (n = 53).
resultsAfter the intervention, DHA-treated APOEɛ3/ɛ3 and APOEɛ2/ɛ3 carriers demonstrated significantly greater increase in plasma DHA/AA compared to ɛ4/ɛ4 carriers. APOEɛ2/ɛ3 had a greater increase in plasma EPA/AA and less decline in left and right hippocampal volumes compared to compared to ɛ4/ɛ4 carriers. The change in plasma and cerebrospinal fluid DHA/AA was strongly correlated. Greater baseline and increase in plasma EPA/AA was associated with a lower decrease in the right hippocampal volume, but only in APOE 4 non-carriers.
conclusionThe lower increase in plasma DHA/AA and EPA/AA in APOEɛ4/ɛ4 carriers after DHA supplementation reduces brain delivery and affects the efficacy of DHA supplementation.
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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 OpenQuestion graph.