Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-β and tau pathology via a mechanism involving presenilin 1 levels
Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-β and tau pathology via a mechanism involving presenilin 1 levels
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DOI：
10.1523/jneurosci.0055-07.2007
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发表时间：
2007-04-18
影响因子：
5.3
通讯作者：
LaFerla, Frank M.
中科院分区：
文献类型：
--
作者：
Green, Kim N.;Martinez-Coria, Hilda;LaFerla, Frank M.
散发性阿尔茨海默病（AD）的根本原因尚不清楚，但可能涉及许多环境和遗传因素。一个越来越被认为是导致大脑衰老的环境因素是饮食，它在现代历史上有着显着的演变。在这里，我们表明，在3xTg-AD小鼠AD模型中，膳食补充二十二碳六烯酸（DHA），一种n-3多不饱和脂肪酸，减少了淀粉样蛋白β（A β）和tau蛋白的神经元内积累。相比之下，将DHA与n-6脂肪酸（花生四烯酸或二十二碳五烯酸（DPAn-6））结合使用，在12个月内降低了DHA的功效。在这里，我们报告的新发现，占可溶性A β的机制是由于减少在稳定状态的早老素1水平的下降，而不是改变加工的淀粉样前体蛋白的α或β分泌酶。此外，饮食中DPAn-6的存在降低了早期磷酸化tau表位的水平，这与磷酸化c-Jun N-末端激酶（一种推定的tau激酶）的减少相关。总的来说，这些结果表明，DHA和DPAn-6的表达可能是一种有益的AD自然疗法。
The underlying cause of sporadic Alzheimer disease ( AD) is unknown, but a number of environmental and genetic factors are likely to be involved. One environmental factor that is increasingly being recognized as contributing to brain aging is diet, which has evolved markedly over modern history. Here we show that dietary supplementation with docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, in the 3xTg-AD mouse model of AD reduced the intraneuronal accumulation of both amyloid-beta(A beta) and tau. In contrast, combining DHA with n-6 fatty acids, either arachidonic acid or docosapentaenoic acid (DPAn-6), diminished the efficacy of DHA over a 12 month period. Here we report the novel finding that the mechanism accounting for the reduction in soluble A beta was attributable to a decrease in steady-state levels of presenilin 1, and not to altered processing of the amyloid precursor protein by either the alpha- or beta-secretase. Furthermore, the presence of DPAn-6 in the diet reduced levels of early-stage phospho-tau epitopes, which correlated with a reduction in phosphorylated c-Jun N-terminal kinase, a putative tau kinase. Collectively, these results suggest that DHA and DPAn-6 supplementations could be a beneficial natural therapy for AD.