Dietary DHA supplementation in an APP/PS1 transgenic rat model of AD reduces behavioral and Aβ pathology and modulates Aβ oligomerization

NEUROBIOLOGY OF DISEASE

卷:82

Article

Teng, Edmond^1,2  Taylor, Karen¹  Bilousova, Tina¹  Weiland, David^1,2  Thaidan Pham¹  Zuo, Xiaohong^1,2,3  Yang, Fusheng^1,2  Chen, Ping-Ping^1,2  Glabe, Charles G.^4,5,6  Takacs, Alison⁷  Hoffman, Dennis R.^7,8  Frautschy, Sally A.^1,2  Cole, Gregory M.^1,2 

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA USA

[2] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA

[3] Capital Med Univ, Xuanwu Hosp, Beijing Inst Geriatr, Dept Neurobiol & Neurol, Beijing, Peoples R China

[4] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA

[5] King Abdulaziz Univ, King Fahd Med Res Ctr, Dept Biochem, Jeddah 21413, Saudi Arabia

[6] King Abdulaziz Univ, King Fahd Med Res Ctr, Expt Biochem Unit, Jeddah 21413, Saudi Arabia

[7] Retina Fdn Southwest, Dallas, TX USA

[8] UT Southwestern Med Ctr, Dept Ophthalmol, Dallas, TX USA

关键词: Docosahexaenoic acid;    beta-amyloid;    Aggregation;    Oligomers;    Fibrillar;    Prefibrillar;    Hippocampus;    Transgenic;    Alzheimer's disease;   

DOI  :  10.1016/j.nbd.2015.09.002

来源: Elsevier

【 摘 要 】

Increased dietary consumption of docosahexaenoic acid (DHA) is associated with decreased risk for Alzheimer's disease (AD). These effects have been postulated to arise from DHA's pleiotropic effects on AD pathophysiology, including its effects on beta-amyloid (A beta) production, aggregation, and toxicity. While in vitro studies suggest that DHA may inhibit and reverse the formation of toxic A beta oligomers, it remains uncertain whether these mechanisms operate in vivo at the physiological concentrations of DHA attainable through dietary supplementation. We sought to clarify the effects of dietary DHA supplementation on A beta indices in a transgenic APP/PS1 rat model of AD. Animals maintained on a DHA-supplemented diet exhibited reductions in hippocampal A beta plaque density and modest improvements on behavioral testing relative to those maintained on a DHA-depleted diet. However, DHA supplementation also increased overall soluble A beta oligomer levels in the hippocampus. Further quantification of specific conformational populations of A beta oligomers indicated that DHA supplementation increased fibrillar (i.e. putatively less toxic) A beta oligomers and decreased prefibrillar (i.e. putatively more toxic) A beta oligomers. These results provide in vivo evidence suggesting that DHA can modulate A beta aggregation by stabilizing soluble fibrillar A beta oligomers and thus reduce the formation of both A beta plaques and prefibrillar AS oligomers. However, since fibrillar A beta oligomers still retain inherent neurotoxicity, DHA may need to be combined with other interventions that can additionally reduce fibrillar A beta oligomer levels for more effective prevention of AD in clinical settings. Published by Elsevier Inc.

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