Early pathologic amyloid induces hypersynchrony of BOLD resting-state networks in transgenic mice and provides an early therapeutic window before amyloid plaque deposition
Early pathologic amyloid induces hypersynchrony of BOLD resting-state networks in transgenic mice and provides an early therapeutic window before amyloid plaque deposition
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DOI：
10.1016/j.jalz.2016.03.010
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发表时间：
2016-09-01
影响因子：
14
通讯作者：
Van der Linden, Annemie
中科院分区：
文献类型：
--
作者：
Shah, Disha;Praet, Jelle;Van der Linden, Annemie
在阿尔茨海默病（AD）中，病理性β淀粉样蛋白（A β）具有突触毒性，在微观尺度上损害神经元功能，在A β沉积之前在宏观尺度上影响脑网络。后者可以使用静息状态功能MRI （rsfMRI）在体内无创检测，这是一种用于评估脑功能连通性（FC）的技术。方法：对TG2576和PDAPP小鼠进行纵向RsfMRI，从All沉积前开始测定最早的FC变化。此外，通过使用3D6抗a β抗体治疗TG2576小鼠，研究病理性All在早期FC改变中的作用。结果：两种转基因模型在All沉积前均表现为高同步的FC，而在后期表现为低同步的FC。TG2576小鼠的早期抗a β治疗可防止超同步FC和相关的突触损伤和兴奋/抑制失衡。讨论：FC的高同步性可以作为早期AD的一种新的无创诊断方法，并且可以通过抗a β治疗来恢复，鼓励家族性AD的预防性治疗策略。(C) 2016年阿尔茨海默病协会。Elsevier Inc.出版。版权所有。
Introduction: In Alzheimer's disease (AD), pathologic amyloid-beta (A beta) is synaptotoxic and impairs neuronal function at the microscale, influencing brain networks at the macroscale before A beta deposition. The latter can be detected noninvasively, in vivo, using resting-state functional MRI (rsfMRI), a technique used to assess brain functional connectivity (FC).Methods: RsfMRI was performed longitudinally in TG2576 and PDAPP mice, starting before All deposition to determine the earliest FC changes. Additionally, the role of pathologic All on early FC alterations was investigated by treating TG2576 mice with the 3D6 anti-A beta-antibody.Results: Both transgenic models showed hypersynchronized FC before All deposition and hypo synchronized FC at later stages. Early anti-A beta treatment in TG2576 mice prevented hypersynchronous FC and the associated synaptic impairments and excitatory/inhibitory disbalances.Discussion: Hypersynchrony of FC may be used as a new noninvasive read out of early AD and can be recovered by anti-A beta treatment, encouraging preventive treatment strategies in familial AD. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.