MoJoe wrote:Two Articles, the first has bad news for APOE4 members, the second has good news showing a workaround to counter the effects of the first article.
Bad News.
Journal of Alzheimer’s Disease 74 (2020) 975–990
DOI 10.3233/JAD-191017
IOS Press
975
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.
Good News
Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer’s disease Rhonda P. Patrick University of California San Francisco Benioff, Children’s Hospital Oakland Research Institute, Oakland, California, USA
ABSTRACT:Dietary and supplemental intake of the Omega 3 fatty acid docosahexaenoic acid (DHA) reduces risk ofAlzheimer’s disease (AD) and ameliorates symptoms. The apolipoprotein E (APOE)4 allele is the strongest risk factor for sporadic AD, exclusive of age. APOE4 carriers respond well to the DHA present in fish but do not respond as well to dietary supplements. The mechanisms behind this varied response remain unknown. I posit that the difference is that fish contain DHA in phospholipid form, whereas fish oil supplements do not. This influences whether DHA is metabolized to nonesterified DHA (free DHA) or a phospholipid form called lysophosphatidylcholine DHA (DHA-lysoPC). Free DHA is transported across the outer membrane leaflet of the blood–brain barrier (BBB) via passive diffusion, and DHA-lysoPC is transported across the inner membrane leaflet of the BBB via the major facilitator superfamily domain-containing protein 2A. I propose that APOE4 carriers have impaired brain transport of free DHA but not of DHA-lysoPC, as a consequence of a breakdown in the outer membrane leaflet of the BBB, putting them at increased risk for AD. Dietary sources of DHA in phospholipid form may provide a means to increase plasmalevels of DHA-lysoPC, thereby decreasing the risk of AD.
MoJoe
Hi Mojoe,
I thought I would save some folks time in finding these two interesting views, and add the abstract and link to the first article, which is an NIH-funded study of DHA in has free access here:
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.
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.
Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease Abstract
Dietary and supplemental intake of the ω-3 fatty acid docosahexaenoic acid (DHA) reduces risk of Alzheimer’s disease (AD) and ameliorates symptoms. The apolipoprotein E (APOE)4 allele is the strongest risk factor for sporadic AD, exclusive of age. APOE4 carriers respond well to the DHA present in fish but do not respond as well to dietary supplements. The mechanisms behind this varied response remain unknown. I posit that the difference is that fish contain DHA in phospholipid form, whereas fish oil supplements do not. This influences whether DHA is metabolized to nonesterified DHA (free DHA) or a phospholipid form called lysophosphatidylcholine DHA (DHA-lysoPC). Free DHA is transported across the outer membrane leaflet of the blood–brain barrier (BBB) via passive diffusion, and DHA-lysoPC is transported across the inner membrane leaflet of the BBB via the major facilitator superfamily domain-containing protein 2A. I propose that APOE4 carriers have impaired brain transport of free DHA but not of DHA-lysoPC, as a consequence of a breakdown in the outer membrane leaflet of the BBB, putting them at increased risk for AD. Dietary sources of DHA in phospholipid form may provide a means to increase plasma levels of DHA-lysoPC, thereby decreasing the risk of AD.—Patrick, R. P. Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer’s disease.
