Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer's disease.
Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer's disease.
复制标题
DOI：
10.1371/journal.pone.0012538
复制
发表时间：
2010-09-08
期刊：
影响因子：
3.7
通讯作者：
Piomelli D
中科院分区：
文献类型：
--
作者：
Astarita G;Jung KM;Berchtold NC;Nguyen VQ;Gillen DL;Head E;Cotman CW;Piomelli D
二十二碳六烯酸（C22：6 n-3）是一种神经营养和神经保护脂肪酸，其脑水平降低可能导致阿尔茨海默病的认知能力下降。在这里，我们调查了在这种疾病中，向大脑提供二十二碳六烯酸的肝酶系统是否功能失调。与对照组相比，阿尔茨海默病患者的颞叶皮层、中额叶皮层和小脑中的二十二碳六烯酸水平降低（P = 0.007）。 简易精神状态检查（MMSE）评分与颞叶皮层（P = 0.005）和中额叶皮层（P = 0.018）的二十二碳六烯酸/α-亚麻酸比值呈正相关，但与小脑无关。 同样，阿尔茨海默病患者的肝脏二十二碳六烯酸含量低于对照组（P = 0.011）。 肝脏二十二碳六烯酸/α-亚麻酸比值与MMSE评分呈正相关（r = 0.78; P<0.0001），与总体恶化量表评分呈负相关（P = 0.013）。 二十二碳六烯酸前体，包括二十四碳六烯酸（C24：6 n-3），在阿尔茨海默病患者的肝脏中升高（P = 0.041），而过氧化物酶体d-双功能蛋白，催化二十四碳六烯酸转化为二十二碳六烯酸的表达减少（P = 0.048）。 其他参与二十二碳六烯酸代谢的基因没有受到影响。结果表明，d-双功能蛋白活性的缺陷损害了阿尔茨海默病患者肝脏中二十二碳六烯酸的生物合成，减少了这种神经保护性脂肪酸向大脑的流动。
Reduced brain levels of docosahexaenoic acid (C22:6n-3), a neurotrophic and neuroprotective fatty acid, may contribute to cognitive decline in Alzheimer's disease. Here, we investigated whether the liver enzyme system that provides docosahexaenoic acid to the brain is dysfunctional in this disease. Docosahexaenoic acid levels were reduced in temporal cortex, mid-frontal cortex and cerebellum of subjects with Alzheimer's disease, compared to control subjects (P = 0.007). Mini Mental State Examination (MMSE) scores positively correlated with docosahexaenoic/α-linolenic ratios in temporal cortex (P = 0.005) and mid-frontal cortex (P = 0.018), but not cerebellum. Similarly, liver docosahexaenoic acid content was lower in Alzheimer's disease patients than control subjects (P = 0.011). Liver docosahexaenoic/α-linolenic ratios correlated positively with MMSE scores (r = 0.78; P<0.0001), and negatively with global deterioration scale grades (P = 0.013). Docosahexaenoic acid precursors, including tetracosahexaenoic acid (C24:6n-3), were elevated in liver of Alzheimer's disease patients (P = 0.041), whereas expression of peroxisomal d-bifunctional protein, which catalyzes the conversion of tetracosahexaenoic acid into docosahexaenoic acid, was reduced (P = 0.048). Other genes involved in docosahexaenoic acid metabolism were not affected. The results indicate that a deficit in d-bifunctional protein activity impairs docosahexaenoic acid biosynthesis in liver of Alzheimer's disease patients, lessening the flux of this neuroprotective fatty acid to the brain.
登录
查看更多内容
DOI：
10.3945/jn.108.096016
发表时间：
2008-12
期刊：
The Journal of nutrition
影响因子：
--
作者：
Lukiw WJ;Bazan NG
通讯作者：
Bazan NG
影响因子：
3.9
作者：
Crawford, Michael A.;Bazinet, Richard P.;Sinclair, Andrew J.
通讯作者：
Sinclair, Andrew J.
DOI：
10.1016/s0006-291x(86)80215-7
发表时间：
1986-12-15
影响因子：
3.1
作者：
BAZAN, NG;SCOTT, BL;PELIAS, MZ
通讯作者：
PELIAS, MZ
影响因子：
4.4
作者：
Fraser, Thomas;Tayler, Hannah;Love, Seth
通讯作者：
Love, Seth
影响因子：
15.9
作者：
Lukiw, WJ;Cui, JG;Bazan, NG
通讯作者：
Bazan, NG