Thin, Stubby or Mushroom: Spine Pathology in Alzheimer's Disease
Thin, Stubby or Mushroom: Spine Pathology in Alzheimer's Disease
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DOI：
10.2174/156720509788486554
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发表时间：
2009-06-01
影响因子：
2.1
通讯作者：
Brandt, R.
中科院分区：
文献类型：
--
作者：
Tackenberg, C.;Ghori, A.;Brandt, R.
自19世纪末Ramon y Cajal首次描述树突以来，树突被认为是神经元接触的重要部位，神经元活动的变化直接影响到脊髓的形态。事实上，从那时起，已经有研究表明，大约90%的兴奋性突触在脊椎上结束。最近的数据表明，脊柱是高度动态的结构，脊柱的形状与突触传递的强度有关。此外，包括阿尔茨海默病(AD)在内的几种精神障碍与脊柱病理有关，这表明脊柱改变在精神缺陷中发挥着核心作用。该综述的目的是提供关于脊柱形态和功能的最新知识，以及分析脊柱变化和动力学的不同实验模型。第二部分集中于与AD相关的疾病相关因素，以及导致脊柱改变的因素。特别是，提供Aβ寡聚体或纤维状Aβ沉积影响脊柱形态和功能的证据的数据将被提出，并将讨论tau病理的贡献。综述最后讨论了与疾病相关的因素如何影响树突棘的潜在机制，以及脊柱变化是否以及如何在治疗上被抑制或逆转。
Since their first description by Ramon y Cajal at the end of the 19th century, dendritic spines have been proposed as important sites of neuronal contacts and it has been suggested that changes in the activity of neurons directly affect spine morphology. In fact, since then it has been shown that about 90% of excitatory synapses end on spines. Recent data indicate that spines are highly dynamic structures and that spine shape correlates with the strength of synaptic transmission. Furthermore, several mental disorders including Alzheimer's disease (AD) are associated with spine pathology suggesting that spine alterations play a central role in mental deficits. The aim of this review is to provide an overview about the current knowledge on spine morphology and function as well as about different experimental models to analyze spine changes and dynamics. The second part concentrates on disease-relevant factors that are associated with AD and which lead to spine alterations. In particular, data that provide evidence that A beta oligomers or fibrillar A beta deposits influence spine morphology and function will be presented and the contribution of tau pathology will be discussed. The review ends with the discussion of potential mechanisms how disease-relevant factors influence dendritic spines and whether and how spine changes could be therapeutically suppressed or reversed.