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DHA brain uptake and APOE4 status: a PET study with [1-(11)C]-DHA
BACKGROUND: The apolipoprotein E ɛ4 (APOE4) allele is the strongest genetic risk factor identified for developing Alzheimer’s disease (AD). Among brain lipids, alteration in the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) homeostasis is implicated in AD pathogenesis. APOE4 may influenc...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364667/ https://www.ncbi.nlm.nih.gov/pubmed/28335828 http://dx.doi.org/10.1186/s13195-017-0250-1 |
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author | Yassine, Hussein N. Croteau, Etienne Rawat, Varun Hibbeln, Joseph R. Rapoport, Stanley I. Cunnane, Stephen C. Umhau, John C. |
author_facet | Yassine, Hussein N. Croteau, Etienne Rawat, Varun Hibbeln, Joseph R. Rapoport, Stanley I. Cunnane, Stephen C. Umhau, John C. |
author_sort | Yassine, Hussein N. |
collection | PubMed |
description | BACKGROUND: The apolipoprotein E ɛ4 (APOE4) allele is the strongest genetic risk factor identified for developing Alzheimer’s disease (AD). Among brain lipids, alteration in the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) homeostasis is implicated in AD pathogenesis. APOE4 may influence both brain DHA metabolism and cognitive outcomes. METHODS: Using positron emission tomography, regional incorporation coefficients (k*), rates of DHA incorporation from plasma into the brain using [1-(11)C]-DHA (J (in)), and regional cerebral blood flow using [(15)O]-water were measured in 22 middle-aged healthy adults (mean age 35 years, range 19–65 years). Data were partially volume error-corrected for brain atrophy. APOE4 phenotype was determined by protein expression, and unesterified DHA concentrations were quantified in plasma. An exploratory post hoc analysis of the effect of APOE4 on DHA brain kinetics was performed. RESULTS: The mean global gray matter DHA incorporation coefficient, k*, was significantly higher (16%) among APOE4 carriers (n = 9) than among noncarriers (n = 13, p = 0.046). Higher DHA incorporation coefficients were observed in several brain regions, particularly in the entorhinal subregion, an area affected early in AD pathogenesis. Cerebral blood flow, unesterified plasma DHA, and whole brain DHA incorporation rate (J (in)) did not differ significantly between the APOE groups. CONCLUSIONS: Our findings suggest an increase in the DHA incorporation coefficient in several brain regions in APOE4 carriers. These findings may contribute to understanding how APOE4 genotypes affect AD risk. |
format | Online Article Text |
id | pubmed-5364667 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-53646672017-03-24 DHA brain uptake and APOE4 status: a PET study with [1-(11)C]-DHA Yassine, Hussein N. Croteau, Etienne Rawat, Varun Hibbeln, Joseph R. Rapoport, Stanley I. Cunnane, Stephen C. Umhau, John C. Alzheimers Res Ther Research BACKGROUND: The apolipoprotein E ɛ4 (APOE4) allele is the strongest genetic risk factor identified for developing Alzheimer’s disease (AD). Among brain lipids, alteration in the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) homeostasis is implicated in AD pathogenesis. APOE4 may influence both brain DHA metabolism and cognitive outcomes. METHODS: Using positron emission tomography, regional incorporation coefficients (k*), rates of DHA incorporation from plasma into the brain using [1-(11)C]-DHA (J (in)), and regional cerebral blood flow using [(15)O]-water were measured in 22 middle-aged healthy adults (mean age 35 years, range 19–65 years). Data were partially volume error-corrected for brain atrophy. APOE4 phenotype was determined by protein expression, and unesterified DHA concentrations were quantified in plasma. An exploratory post hoc analysis of the effect of APOE4 on DHA brain kinetics was performed. RESULTS: The mean global gray matter DHA incorporation coefficient, k*, was significantly higher (16%) among APOE4 carriers (n = 9) than among noncarriers (n = 13, p = 0.046). Higher DHA incorporation coefficients were observed in several brain regions, particularly in the entorhinal subregion, an area affected early in AD pathogenesis. Cerebral blood flow, unesterified plasma DHA, and whole brain DHA incorporation rate (J (in)) did not differ significantly between the APOE groups. CONCLUSIONS: Our findings suggest an increase in the DHA incorporation coefficient in several brain regions in APOE4 carriers. These findings may contribute to understanding how APOE4 genotypes affect AD risk. BioMed Central 2017-03-23 /pmc/articles/PMC5364667/ /pubmed/28335828 http://dx.doi.org/10.1186/s13195-017-0250-1 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Yassine, Hussein N. Croteau, Etienne Rawat, Varun Hibbeln, Joseph R. Rapoport, Stanley I. Cunnane, Stephen C. Umhau, John C. DHA brain uptake and APOE4 status: a PET study with [1-(11)C]-DHA |
title | DHA brain uptake and APOE4 status: a PET study with [1-(11)C]-DHA |
title_full | DHA brain uptake and APOE4 status: a PET study with [1-(11)C]-DHA |
title_fullStr | DHA brain uptake and APOE4 status: a PET study with [1-(11)C]-DHA |
title_full_unstemmed | DHA brain uptake and APOE4 status: a PET study with [1-(11)C]-DHA |
title_short | DHA brain uptake and APOE4 status: a PET study with [1-(11)C]-DHA |
title_sort | dha brain uptake and apoe4 status: a pet study with [1-(11)c]-dha |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364667/ https://www.ncbi.nlm.nih.gov/pubmed/28335828 http://dx.doi.org/10.1186/s13195-017-0250-1 |
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