Ovsepian Saak V, O'Leary Valerie B
International Centre for Neurotherapeutics, Dublin City University, Dublin, Republic of Ireland.
Institute of Radiation Biology, Helmholtz Zentrum Munich, Neuherberg, Germany.
J Alzheimers Dis. 2016;49(1):13-9. doi: 10.3233/JAD-150544.
A breakthrough in Alzheimer's disease (AD) research came with the discovery of the link between activity-dependent release of amyloid-β (Aβ) from neurons and formation of amyloid plaques. Along with elucidating the cellular basis of behavioral-dependent fluctuations in Aβ levels in the brain, insights have been gained toward understanding the mechanisms that warrant selective vulnerability of various forebrain circuits to amyloid pathology. The notion of elevated activity as a source of excessive Aβ production and plaque formation is, however, in conflict with ample electrophysiological data, which demonstrate exceedingly intense activity (both intrinsic and synaptic) of neurons in several brain regions that are spared or marginally affected by amyloid plaques of AD. Thus, the link between the functional load of brain circuits and their vulnerability to amyloidosis, while evident, is also complex and remains poorly understood. Here, we discuss emerging data suggestive of a major role for super-intense synchronous activity of cortical and limbic networks in excessive Aβ production and plaque formation. It is proposed that dense recurrent wiring of associative areas prone to epileptic seizures might be of critical relevance to their higher susceptibility to plaque pathology and related functional impairments.
阿尔茨海默病（AD）研究的一项突破是发现了神经元中淀粉样β蛋白（Aβ）的活性依赖性释放与淀粉样斑块形成之间的联系。在阐明大脑中Aβ水平行为依赖性波动的细胞基础的同时，对于理解各种前脑回路对淀粉样病变具有选择性易损性的机制也有了深入认识。然而，将活动增强视为过量Aβ产生和斑块形成的来源这一观点，与大量电生理数据相矛盾，这些数据表明，在AD淀粉样斑块 spared或仅受到轻微影响的几个脑区中，神经元具有极其强烈的活动（包括内在活动和突触活动）。因此，脑回路的功能负荷与其对淀粉样变性的易损性之间的联系虽然明显，但也很复杂，仍知之甚少。在此，我们讨论新出现的数据，这些数据表明皮层和边缘网络的超强同步活动在过量Aβ产生和斑块形成中起主要作用。有人提出，易于发生癫痫发作的联合区域的密集递归布线可能与其对斑块病变和相关功能障碍的更高易感性密切相关。
