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Reduction in DHA transport to the brain of mice expressing human APOE 4 compared to APOE 2
Author(s) -
Vandal Milène,
Alata Wael,
Tremblay Cyntia,
RiouxPerreault Christine,
Salem Norman,
Calon Frédéric,
Plourde Mélanie
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12640
Subject(s) - apolipoprotein e , docosahexaenoic acid , endocrinology , medicine , biology , neurodegeneration , cerebral cortex , genetically modified mouse , biochemistry , chemistry , fatty acid , transgene , polyunsaturated fatty acid , disease , gene
Benefits on cognition from docosahexaenoic acid ( DHA , 22 : 6 n‐3) intake are absent in humans carrying apolipoprotein E ε4 allele ( APOE 4 ), the most important genetic risk factor for Alzheimer's disease ( AD ). To test the hypothesis that carrying APOE 4 impairs DHA distribution, we evaluated plasma and brain fatty acid profiles and uptake of [ 14 C]‐ DHA using in situ cerebral perfusion through the blood–brain barrier in 4‐ and 13‐month‐old male and female APOE ‐targeted replacement mice ( APOE 2 , APOE 3 , and APOE 4 ), fed with a DHA ‐depleted diet. Cortical and plasma DHA were 9% lower and 34% higher in APOE 4 compared to APOE 2 mice, respectively. Brain uptake of [ 14 C]‐ DHA was 24% lower in APOE 4 versus APOE 2 mice. A significant relationship was established between DHA and apoE concentrations in the cortex of mice ( r 2 = 0.21) and AD patients ( r 2 = 0.32). Altogether, our results suggest that lower brain uptake of DHA in APOE 4 than in APOE 2 mice may limit the accumulation of DHA in cerebral tissues. These data provide a mechanistic explanation for the lack of benefit of DHA in APOE 4 carriers on cognitive function and the risk of AD .Using human APOE2 , 3 , and 4 isoform‐specific transgenic mice, we found a lower brain uptake of docosahexaenoic acid (DHA) in APOE4 than in APOE2 mice that may limit the biodistribution of DHA in cerebral tissues. These data provide a mechanistic explanation for the lack of benefit of DHA in APOE4 carriers on cognitive function and the risk of Alzheimer's disease (AD).