Department of Experimental Neurology, Laboratory of Psychobiology, Santa Lucia Foundation, Via del Fosso di Fiorano, 00143 Rome, Italy.
Institute of Cell Biology and Neurobiology, National Research Centre, Via E. Ramarini, Monterotondo, 00040 Rome, Italy.
Neural Plast. 2017;2017:5281829. doi: 10.1155/2017/5281829. Epub 2017 Dec 24.
Neuronal activity has a strong causal role in the production and release of the neurotoxic -amyloid peptide (A). Because of this close link, gradual accumulation of A into amyloid plaques has been reported in brain areas with intense neuronal activity, including cortical regions that display elevated activation at resting state. However, the link between A and activity is not always linear and recent studies report exceptions to the view of "more activity, more plaques." Here, we review the literature about the activity-dependent production of A in both human cases and AD models and focus on the evidences that brain regions with elevated convergence of synaptic connections (herein referred to as brain nodes) are particularly vulnerable to A accumulation. Next, we will examine data supporting the hypothesis that, since A is released from synaptic terminals, -amyloidosis can spread in AD brain by advancing through synaptically connected regions, which makes brain nodes vulnerable to A accumulation. Finally, we consider possible mechanisms that account for -amyloidosis progression through synaptically linked regions.
神经元活动在神经毒性淀粉样肽 (A) 的产生和释放中起着重要的因果作用。由于这种密切的联系，据报道，在神经元活动强烈的大脑区域，包括在静息状态下显示出激活增加的皮质区域，A 逐渐积累成淀粉样斑块。然而，A 与活动之间的联系并不总是线性的，最近的研究报告了“更多的活动，更多的斑块”这一观点的例外情况。在这里，我们回顾了关于人类病例和 AD 模型中 A 的活性依赖性产生的文献，并重点关注了支持以下观点的证据：即具有高突触连接汇聚的大脑区域（在此称为大脑节点）特别容易受到 A 积累的影响。接下来，我们将研究支持以下假设的数据：由于 A 从突触末梢释放，因此在 AD 大脑中，-淀粉样蛋白可以通过连接的突触区域向前推进而传播，从而使大脑节点容易受到 A 积累的影响。最后，我们考虑了可能的机制，这些机制解释了通过突触连接区域的 -淀粉样蛋白病进展。
