Three dimensions of the amyloid hypothesis: time, space and 'wingmen'.
Three dimensions of the amyloid hypothesis: time, space and 'wingmen'.
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DOI：
10.1038/nn.4018
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发表时间：
2015-06
影响因子：
25
通讯作者：
Holtzman, David M.
中科院分区：
文献类型：
--
作者：
Musiek, Erik S.;Holtzman, David M.
淀粉样蛋白假说是过去二十年来阿尔茨海默病（AD）研究的主要框架，也是该领域内相当大的争议的来源。淀粉样蛋白假说假定淀粉样蛋白β肽（Aβ）是AD的致病因子，并得到罕见常染色体显性形式AD数据的有力支持。然而，Aβ导致年龄相关的散发性AD的证据更加复杂且不太清楚，这促使了对该假设的批评。在此，我们提供了一个主要的参数支持和反对淀粉样蛋白假说的概述，并审查支持或反驳这些论点的关键数据。我们的结论是，Aβ可能是导致AD的复杂致病级联反应的关键启动子，从而支持淀粉样蛋白假说。然而，我们认为Aβ主要是作为其他下游过程的触发剂，特别是介导神经退行性变的tau聚集。因此，Aβ似乎是导致AD的必要因素，但不足以导致AD，其主要致病作用可能发生在疾病过程的非常早期。我们讨论了治疗发展和未来研究的影响。
The Amyloid Hypothesis, which has been the predominant framework for research in Alzheimer’s Disease (AD) over the past two decades, has also been the source of considerable controversy within the field. The Amyloid Hypothesis postulates that amyloid-beta peptide (Aβ) is the causative agent in AD, and is strongly supported by data from rare autosomal dominant forms of AD. However, the evidence that Aβ causes age-associated sporadic AD is more complex and less clear, prompting criticism of the hypothesis. Herein, we provide an overview of the major arguments for and against the Amyloid Hypothesis, and review key data supporting or refuting these arguments. We conclude that Aβ likely is the key initiator of a complex pathogenic cascade which causes AD, thus supporting the Amyloid Hypothesis in general. However, we argue that Aβ acts primarily as a trigger of other downstream processes, in particular tau aggregation, which mediate neurodegeneration. Thus, Aβ appears to be necessary but not sufficient to causes AD, and its major pathogenic effects may occur very early in the disease process. We discuss implications for therapeutic development and future research.
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影响因子：
29
作者：
Donohue, Michael C.;Sperling, Reisa A.;Salmon, David P.;Rentz, Dorene M.;Raman, Rema;Thomas, Ronald G.;Weiner, Michael;Aisen, Paul S.
通讯作者：
Aisen, Paul S.
DOI：
10.1523/jneurosci.0033-12.2012
发表时间：
2012-04-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bien-Ly N;Gillespie AK;Walker D;Yoon SY;Huang Y
通讯作者：
Huang Y
影响因子：
12.7
作者：
Braak, Heiko;Del Tredici, Kelly
通讯作者：
Del Tredici, Kelly
影响因子：
4.2
作者：
Benzing, WC;Wujek, JR;Brunden, KR
通讯作者：
Brunden, KR
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