CR1 and the "vanishing amyloid" hypothesis of Alzheimer's disease.
CR1 and the "vanishing amyloid" hypothesis of Alzheimer's disease.
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DOI：
10.1016/j.biopsych.2013.01.013
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发表时间：
2013-03-01
影响因子：
10.6
通讯作者：
Schadt, Eric E.
中科院分区：
文献类型：
--
作者：
Gandy, Sam;Haroutunian, Vahram;DeKosky, Steven T.;Sano, Mary;Schadt, Eric E.
在政治和经济领域，“黑天鹅”事件是指极不可能发生、不可预见、千载难逢的事态发展，它们的力量如此强大，以至于会在选举轨迹或一个国家的财政状况中造成意想不到但持久的变化。在生物学中，黑天鹅事件改变了我们对可能性的看法，向我们指出了新的解释，把我们带到了新的和以前没有考虑过的方向。阿尔茨海默病研究中最近的黑天鹅事件发生在2012年中期，冰岛发现阿尔茨海默病淀粉样蛋白前体蛋白（APP）突变，该突变显著降低了β位点APP切割酶裂解APP的催化效率，这是淀粉样蛋白β (a β)生成的限速步骤[回顾，见(1)]。在受孕时携带这种冰岛APP突变的人显然注定会正常生活和发育，但更重要的是，即使他们携带两份高风险载脂蛋白E (APOE) ε4等位基因，他们也不会在晚年患上阿尔茨海默病（AD），这种情况通常与大脑淀粉样变性增强和AD风险增加10倍有关。
In politics and economics,“black swan” events are highly improbable, unforeseeable, oncein-a-lifetime developments that are so powerful as to cause unexpected but long-lasting changes in the trajectory of an election or of a country’s fiscal status. In biology, black swan events change our view of the possible, pointing us toward novel interpretations that take us in new and previously unconsidered directions.The most recent black swan event in Alzheimer’s research occurred in mid-2012 with the discovery in Iceland of a mutation in the Alzheimer’s amyloid precursor protein (APP) that dramatically reduces the catalytic efficiency of cleavage of APP by beta-site APP-cleaving enzyme, the rate-limiting step in amyloid-beta (Aβ) generation [for review, see (1)]. Persons blessed with this Icelandic APP mutation at the time of their conception are apparently destined to live and develop normally, but, more importantly, they are protected from the development of Alzheimer’s disease (AD) in late life, even if they harbor two copies of the high-risk apolipoprotein E (APOE) ε4 allele, a situation that usually associates with enhanced cerebral amyloidosis and a 10-fold increase in AD risk.
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DOI：
10.1093/gerona/gls103
发表时间：
2012-11-01
影响因子：
5.1
作者：
Huffman, Derek M.;Deelen, Joris;Atzmon, Gil
通讯作者：
Atzmon, Gil
影响因子：
10.5
作者：
Gandy S;DeKosky ST
通讯作者：
DeKosky ST
影响因子：
10.6
作者：
Thambisetty, Madhav;An, Yang;Nalls, Michael;Sojkova, Jitka;Swaminathan, Shanker;Zhou, Yun;Singleton, Andrew B.;Wong, Dean F.;Ferrucci, Luigi;Saykin, Andrew J.;Resnick, Susan M.
通讯作者：
Resnick, Susan M.
影响因子：
9.8
作者：
Zhu J;Sova P;Xu Q;Dombek KM;Xu EY;Vu H;Tu Z;Brem RB;Bumgarner RE;Schadt EE
通讯作者：
Schadt EE
影响因子：
9.9
作者：
Scholl, Michael;Wall, Anders;Nordberg, Agneta
通讯作者：
Nordberg, Agneta