Effect of apolipoprotein E genotype and diet on apolipoprotein E lipidation and amyloid peptides: randomized clinical trial.
Effect of apolipoprotein E genotype and diet on apolipoprotein E lipidation and amyloid peptides: randomized clinical trial.
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DOI：
10.1001/jamaneurol.2013.396
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发表时间：
2013-08
期刊：
影响因子：
29
通讯作者：
Craft, Suzanne
中科院分区：
文献类型：
--
作者：
Hanson, Angela J.;Bayer-Carter, Jennifer L.;Green, Pattie S.;Montine, Thomas J.;Wilkinson, Charles W.;Baker, Laura D.;Watson, Stennis;Bonner, Laura M.;Callaghan, Maureen;Leverenz, James B.;Tsai, Elaine;Postupna, Nadia;Zhang, Jing;Lampe, Johanna;Craft, Suzanne
散发性阿尔茨海默病（AD）部分是由于β-淀粉样蛋白（Aβ）肽分解产物的清除减少引起的。脂质耗竭（LD）载脂蛋白结合和清除Aβ的效果较差，LD Aβ肽对神经元的毒性更大。然而，对人类脑脊液中这些蛋白质的脂质状态知之甚少。在认知诊断和APOE ε4等位基因携带状态以及饮食干预后，描述成人脑脊液中Aβ肽和载脂蛋白E的脂化状态。随机临床试验。退伍军人事务医疗中心临床研究单位。20例认知正常的老年人（平均[SD]年龄，69 [7]岁）和27例遗忘型轻度认知障碍（67 [6]岁）。随机分配至饱和脂肪含量高且血糖指数高的饮食（高饮食;45%的能量来自脂肪[>25%饱和脂肪]，35%-40%来自碳水化合物，平均血糖指数>70，15%-20%来自蛋白质）或饱和脂肪含量低且血糖指数低的饮食（低饮食; 25%的能量来自脂肪[<7%饱和脂肪]，55%-60%来自碳水化合物，平均血糖指数<55，15%-20%来自蛋白质）。脑脊液中脂质耗竭的Aβ42和Aβ40以及载脂蛋白E。轻度认知功能障碍的成人LD Aβ基线水平高于认知功能正常的成人（LD Aβ42，P=.05; LD Aβ40，P=.01）。这些结果在轻度认知功能障碍和ε4等位基因的成人中被放大，他们的LD载脂蛋白E水平较高，而与认知功能诊断无关（P<.001）。低水平饮食倾向于降低LD Aβ水平，而高水平饮食增加了这些分数（LD Aβ42，P= 0.01; LD Aβ40，P= 0.15）。低水平饮食的LD Aβ水平变化与脑脊液胰岛素水平变化呈负相关（LD Aβ42和胰岛素，r=-0.68 [P=.01]; LD Aβ40和胰岛素，r=-0.78 [P=.002]）。脑中载脂蛋白和Aβ肽的脂化状态因APOE基因型和认知诊断而异。浓度可通过饮食调节。这些发现可能有助于深入了解载脂蛋白E4和不健康饮食导致AD风险的机制。
Sporadic Alzheimer disease (AD) is caused in part by decreased clearance of the β-amyloid (Aβ) peptide breakdown products. Lipid-depleted (LD) apolipoproteins are less effective at binding and clearing Aβ, and LD Aβ peptides are more toxic to neurons. However, not much is known about the lipid states of these proteins in human cerebrospinal fluid. To characterize the lipidation states of Aβ peptides and apolipoprotein E in the cerebrospinal fluid in adults with respect to cognitive diagnosis and APOE ε4 allele carrier status and after a dietary intervention. Randomized clinical trial. Veterans Affairs Medical Center clinical research unit. Twenty older adults with normal cognition (mean [SD] age, 69 [7] years) and 27 with amnestic mild cognitive impairment (67 [6] years). Randomization to a diet high in saturated fat content and with a high glycemic index (High diet;45% of energy from fat [>25% saturated fat], 35%-40%fromcarbohydrates with a mean glycemic index >70, and15%-20% from protein) or a diet low in saturated fat content and with a low glycemic index (Low diet; 25% of energy from fat [<7% saturated fat], 55%-60% from carbohydrates with a mean glycemic index <55, and 15%-20% from protein). Lipid-depleted Aβ42 and Aβ40 and apolipoprotein E in cerebrospinal fluid. Baseline levels of LD Aβ were greater for adults with mild cognitive impairment compared with adults with normal cognition (LD Aβ42, P=.05; LD Aβ40, P=.01).These findings were magnified in adults with mild cognitive impairment and the ε4 allele, who had higher LD apolipoprotein E levels irrespective of cognitive diagnosis (P<.001). The Low diet tended to decrease LD Aβ levels, whereas the High diet increased these fractions (LD Aβ42, P=.01; LD Aβ40, P=.15). Changes in LD Aβ levels with the Low diet negatively correlated with changes in cerebrospinal fluid levels of insulin (LD Aβ42 and insulin, r= −0.68 [P=.01]; LD Aβ40 and insulin, r= −0.78 [P=.002]). The lipidation states of apolipoproteins and Aβ peptides in the brain differ depending on APOE genotype and cognitive diagnosis. Concentrations can be modulated by diet. These findings may provide insight into the mechanisms through which apolipoprotein E4 and unhealthy diets impart risk for developing AD.
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影响因子：
4.4
作者：
Hesse, C;Larsson, H;Blennow, K
通讯作者：
Blennow, K
影响因子：
12.7
作者：
Arold S;Sullivan P;Bilousova T;Teng E;Miller CA;Poon WW;Vinters HV;Cornwell LB;Saing T;Cole GM;Gylys KH
通讯作者：
Gylys KH
DOI：
10.1126/science.1217697
发表时间：
2012-03-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cramer PE;Cirrito JR;Wesson DW;Lee CY;Karlo JC;Zinn AE;Casali BT;Restivo JL;Goebel WD;James MJ;Brunden KR;Wilson DA;Landreth GE
通讯作者：
Landreth GE
DOI：
10.1073/pnas.0809158106
发表时间：
2009-02-10
影响因子：
11.1
作者：
De Felice, Fernanda G.;Vieira, Marcelo N. N.;Klein, William L.
通讯作者：
Klein, William L.
影响因子：
13.6
作者：
Hauser, Paul S.;Narayanaswami, Vasanthy;Ryan, Robert O.
通讯作者：
Ryan, Robert O.