Early pathologic amyloid induces hypersynchrony of BOLD resting-state networks in transgenic mice and provides an early therapeutic window before amyloid plaque deposition

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.