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
Tomaszewski N, He X, Solomon V, Lee M, Mack WJ, Quinn JF, Braskie MN, Yassine HN
Journal of Alzheimer's disease : JAD · 56 citations
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- National Institute on Aging
- Government
- NIA NIH HHS
- Grants
- National Institute on Aging (R01 AG055770); National Institute on Aging (P50 AG005142); National Institute on Aging (P30-AG066530); National Institute on Aging (R21 AG056518); National Institute on Aging (R01 AG054434)
Based on 2 listed funder(s).
Publication
- Published
- 2020-02-28 · J Alzheimers Dis · vol. 74 · issue 3 · pp. 975–990
- Publisher
- IOS Press
- Cited
- 76 citations · more than 97% of similar papers · 5.1× the field average
- Impact
- Top 10% most cited in its field
- References
- 47 works
- Access
- Open access (repository copy)
- Research areas
- Fatty Acid Research and Health · Eicosanoids and Hypertension Pharmacology · Antioxidant Activity and Oxidative Stress
- Keywords
- Docosahexaenoic acid, Eicosapentaenoic acid, Apolipoprotein E, Internal medicine, Arachidonic acid, Polyunsaturated fatty acid, Endocrinology, Medicine, Docosapentaenoic acid, Placebo, Fatty acid, Chemistry, Biochemistry, Pathology, Disease
- MeSH
- hippocampus, humans, alzheimer disease, fatty acids, omega-3, docosahexaenoic acids, eicosapentaenoic acid, fatty acids, arachidonic acid, apolipoproteins e, magnetic resonance imaging, sex characteristics, genotype, dietary supplements, aged, middle aged, female, male
8 authors
From US
- Natalie TomaszewskiUniversity of Southern California
- Xulei HeUniversity of Southern California
- Victoria A. SolomonUniversity of Southern California
- Mitchell B. LeeUniversity of Southern California
- Wendy Jean MackUniversity of Southern California
- Joseph F. QuinnOregon Health & Science University; Portland VA Medical Center
Abstract
Background
Docosahexaenoic 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.
Objective
We 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.
Methods
Plasma 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).
Results
After 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.
Conclusion
The 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.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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