以色列特拉维夫大学生理学家伊娜·斯卢特斯基博士领导的研究小组发现，β淀粉状蛋白除可引发老年痴呆外，还具有调节大脑神经键间信号传输的作用，只有其含量保持平衡，神经网络才能正常工作，过多或过少都可引发老年痴呆。

此前研究显示，β淀粉状蛋白是一种与老年痴呆有关的有毒物质。斯卢特斯基博士在实验中发现了这种蛋白质在大脑中发挥作用的分子机制。研究显示，过量β淀粉状蛋白会导致神经键数量下降，影响大脑中负责学习和记忆区域的分子功能；一旦大脑中的β淀粉状蛋白开始大量聚集，引发老年痴呆的过程将很难逆转，即使将其清除也没太大作用，因此，必须在其大量产生的初期加以控制，如等到这种蛋白质大量聚集再采取措施就为时过晚了。

与此同时，研究人员还惊奇地发现，β淀粉状蛋白具有在健康大脑神经间传递信息的重要作用，如果这种蛋白质显著下降，同样会损害分子功能。这表明，大脑神经网络与β淀粉状蛋白存在某种经过优化的平衡关系，以确保信息的顺利传递，该蛋白质太多或太少都会打破这种平衡。研究人员表示，他们将进一步研究这一机制，以便开发出一种防止这种蛋白质过量聚集的药物，而不是仅仅将其摧毁。

原始出处：

Nature Neuroscience 12, 1567 - 1576 (2009) 22 November 2009 | doi:10.1038/nn.2433

Amyloid-β as a positive endogenous regulator of release probability at hippocampal synapses

Efrat Abramov1,3, Iftach Dolev1,3, Hilla Fogel1, Giuseppe D Ciccotosto2, Eyal Ruff1 & Inna Slutsky1

Accumulation of cerebral amyloid- peptide (Aβ) is essential for developing synaptic and cognitive deficits in Alzheimer's disease. However, the physiological functions of A, as well as the primary mechanisms that initiate early A-mediated synaptic dysfunctions, remain largely unknown. Here we examine the acute effects of endogenously released Aβ peptides on synaptic transfer at single presynaptic terminals and synaptic connections in rodent hippocampal cultures and slices. Increasing extracellular Aβ by inhibiting its degradation enhanced release probability, boosting ongoing activity in the hippocampal network. Presynaptic enhancement mediated by Aβ was found to depend on the history of synaptic activation, with lower impact at higher firing rates. Notably, both elevation and reduction in Aβ levels attenuated short-term synaptic facilitation during bursts in excitatory synaptic connections. These observations suggest that endogenous Aβ peptides have a crucial role in activity-dependent regulation of synaptic vesicle release and might point to the primary pathological events that lead to compensatory synapse loss in Alzheimer's disease.

1 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
2 Department of Pathology, Bio21 Molecular Science and Biotechnology Institute and Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia.
3 These authors contributed equally to this work.