Toward the treatment and prevention of Alzheimer's disease: rational strategies and recent progress.
Toward the treatment and prevention of Alzheimer's disease: rational strategies and recent progress.
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DOI：
10.1146/annurev-med-092611-084441
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发表时间：
2013
影响因子：
10.5
通讯作者：
DeKosky ST
中科院分区：
文献类型：
--
作者：
Gandy S;DeKosky ST
阿尔茨海默病（AD）是导致老年脑功能衰竭的主要原因。在过去的25年中，发现常染色体显性形式的AD主要可归因于两种早老素中的一种的突变，早老素是多位蛋白，其含有释放淀粉样蛋白β（Aβ）肽的γ-分泌酶蛋白酶的催化位点。一些家族性AD也是由于淀粉样前体蛋白（APP）的突变，但最近发现APP的突变减少了Aβ的产生并对AD具有保护作用，进一步涉及淀粉样代谢。淀粉样纤维和神经纤维缠结的朊病毒样播种已被用来解释AD在脑内的典型传播。使用抗A β抗体的治疗试验已经显示出靶向接合，如果不是显著的治疗效果的话。人们越来越关注症状前的干预，因为Aβ代谢不良在症状开始前25年就开始了。来自新生物信息的AD试验涉及非凡的国际合作，可能是对抗AD取得成功的最大希望。
Alzheimer’s disease (AD) is the major cause of late-life brain failure. In the past 25 years, autosomal dominant forms of AD were found to be primariy attributable to mutations in one of two presenilins, polytopic proteins that contain the catalytic site of the γ-secretase protease that releases the amyloid beta (Aβ) peptide. Some familial AD is also due to mutations in the amyloid precursor protein (APP), but recently a mutation in APP was discovered that reduces Aβ generation and is protective against AD, further implicating amyloid metabolism. Prion-like seeding of amyloid fibrils and neurofibrillary tangles has been invoked to explain the stereotypical spread of AD within the brain. Treatment trials with anti-Aβ antibodies have shown target engagement, if not significant treatment effects. Attention is increasingly focused on presymptomatic intervention, because Aβ mismetabolism begins up to 25 years before symptoms begin. AD trials deriving from new biological information involve extraordinary international collaboration and may hold the best hope for success in the fight against AD.
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影响因子：
--
作者：
De Meyer, Geert;Shapiro, Fred;Vanderstichele, Hugo;Vanmechelen, Eugeen;Engelborghs, Sebastiaan;De Deyn, Peter Paul;Coart, Els;Hansson, Oskar;Minthon, Lennart;Zetterberg, Henrik;Blennow, Kaj;Shaw, Leslie;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
5.3
作者：
Fjorback, Anja W.;Seaman, Matthew;Andersen, Olav M.
通讯作者：
Andersen, Olav M.
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
影响因子：
16.2
作者：
de Calignon A;Polydoro M;Suárez-Calvet M;William C;Adamowicz DH;Kopeikina KJ;Pitstick R;Sahara N;Ashe KH;Carlson GA;Spires-Jones TL;Hyman BT
通讯作者：
Hyman BT
影响因子：
--
作者：
Gabel, Matthew J.;Foster, Norman L.;Zamrini, Edward Y.
通讯作者：
Zamrini, Edward Y.