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Endogenous conversion of omega-6 into omega-3 fatty acids improves neuropathology in an animal model of Alzheimer's disease.
J Alzheimers Dis 2011; 27(4):853-69JA

Abstract

Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) reduces amyloid-β (Aβ) and tau pathology and improves cognitive performance in animal models of Alzheimer's disease (AD). To exclude confounding variables associated with the diet, we crossed 3 × Tg-AD mice (modeling AD neuropathology) with transgenic Fat-1 mice that express the fat-1 gene encoding a PUFA desaturase, which endogenously produces n-3 PUFA from n-6 PUFA. The expression of fat-1 shifted the n-3:n-6 PUFA ratio upward in the brain (+11%, p < 0.001), including docosahexaenoic acid (DHA; +5%, p < 0.001) in 20 month-old mice. The expression of fat-1 decreased the levels of soluble Aβ₄₂ (-41%, p < 0.01) at 20 months without reducing the level of insoluble forms of Aβ₄₀ and Aβ₄₂ in the brain of 3 × Tg-AD mice. The 3 × Tg-AD/Fat-1 mice exhibited lower cortical levels of both soluble (-25%, p < 0.05) and insoluble phosphorylated tau (-55%, p < 0.05) compared to 3 × Tg-AD mice, but only in 20 month-old animals. Whereas a decrease of calcium/calmodulin-dependent protein kinase II was observed in 3 × Tg-AD/Fat-1 mice (-039%, p < 0.05), altered tau phosphorylation could not be related to changes in glycogen synthase kinase 3β, cyclin-dependent kinase 5, or protein phosphatase type 2A enzymatic activity. In addition, the expression of the fat-1 transgene prevented the increase of glial fibrillary acidic protein (-37%, p < 0.01) observed in 20 month-old 3 × Tg-AD mice. In conclusion, the expression of fat-1 in 3 × Tg-AD mice increases brain DHA and induces biomarker changes that are consistent with a beneficial effect against an AD-like neuropathology.

Authors+Show Affiliations

Faculty of Pharmacy, Laval University, Quebec, QC, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21914946

Citation

Lebbadi, Meryem, et al. "Endogenous Conversion of Omega-6 Into Omega-3 Fatty Acids Improves Neuropathology in an Animal Model of Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 27, no. 4, 2011, pp. 853-69.
Lebbadi M, Julien C, Phivilay A, et al. Endogenous conversion of omega-6 into omega-3 fatty acids improves neuropathology in an animal model of Alzheimer's disease. J Alzheimers Dis. 2011;27(4):853-69.
Lebbadi, M., Julien, C., Phivilay, A., Tremblay, C., Emond, V., Kang, J. X., & Calon, F. (2011). Endogenous conversion of omega-6 into omega-3 fatty acids improves neuropathology in an animal model of Alzheimer's disease. Journal of Alzheimer's Disease : JAD, 27(4), pp. 853-69. doi:10.3233/JAD-2011-111010.
Lebbadi M, et al. Endogenous Conversion of Omega-6 Into Omega-3 Fatty Acids Improves Neuropathology in an Animal Model of Alzheimer's Disease. J Alzheimers Dis. 2011;27(4):853-69. PubMed PMID: 21914946.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endogenous conversion of omega-6 into omega-3 fatty acids improves neuropathology in an animal model of Alzheimer's disease. AU - Lebbadi,Meryem, AU - Julien,Carl, AU - Phivilay,Alix, AU - Tremblay,Cyntia, AU - Emond,Vincent, AU - Kang,Jing X, AU - Calon,Frédéric, PY - 2011/9/15/entrez PY - 2011/9/15/pubmed PY - 2012/4/17/medline SP - 853 EP - 69 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 27 IS - 4 N2 - Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) reduces amyloid-β (Aβ) and tau pathology and improves cognitive performance in animal models of Alzheimer's disease (AD). To exclude confounding variables associated with the diet, we crossed 3 × Tg-AD mice (modeling AD neuropathology) with transgenic Fat-1 mice that express the fat-1 gene encoding a PUFA desaturase, which endogenously produces n-3 PUFA from n-6 PUFA. The expression of fat-1 shifted the n-3:n-6 PUFA ratio upward in the brain (+11%, p < 0.001), including docosahexaenoic acid (DHA; +5%, p < 0.001) in 20 month-old mice. The expression of fat-1 decreased the levels of soluble Aβ₄₂ (-41%, p < 0.01) at 20 months without reducing the level of insoluble forms of Aβ₄₀ and Aβ₄₂ in the brain of 3 × Tg-AD mice. The 3 × Tg-AD/Fat-1 mice exhibited lower cortical levels of both soluble (-25%, p < 0.05) and insoluble phosphorylated tau (-55%, p < 0.05) compared to 3 × Tg-AD mice, but only in 20 month-old animals. Whereas a decrease of calcium/calmodulin-dependent protein kinase II was observed in 3 × Tg-AD/Fat-1 mice (-039%, p < 0.05), altered tau phosphorylation could not be related to changes in glycogen synthase kinase 3β, cyclin-dependent kinase 5, or protein phosphatase type 2A enzymatic activity. In addition, the expression of the fat-1 transgene prevented the increase of glial fibrillary acidic protein (-37%, p < 0.01) observed in 20 month-old 3 × Tg-AD mice. In conclusion, the expression of fat-1 in 3 × Tg-AD mice increases brain DHA and induces biomarker changes that are consistent with a beneficial effect against an AD-like neuropathology. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/21914946/Endogenous_conversion_of_omega_6_into_omega_3_fatty_acids_improves_neuropathology_in_an_animal_model_of_Alzheimer's_disease_ L2 - https://content.iospress.com/openurl?genre=article&amp;id=doi:10.3233/JAD-2011-111010 DB - PRIME DP - Unbound Medicine ER -