Early pathologic amyloid induces hypersynchrony of BOLD resting-state networks in transgenic mice and provides an early therapeutic window before amyloid plaque deposition.
In Alzheimer's disease (AD), pathologic amyloid-beta (Aβ) is synaptotoxic and impairs neuronal function at the microscale, influencing brain networks at the macroscale before Aβ deposition. The latter can be detected noninvasively, in vivo, using resting-state functional MRI (rsfMRI), a technique used to assess brain functional connectivity (FC).



RsfMRI was performed longitudinally in TG2576 and PDAPP mice, starting before Aβ deposition to determine the earliest FC changes. Additionally, the role of pathologic Aβ on early FC alterations was investigated by treating TG2576 mice with the 3D6 anti-Aβ-antibody.



Both transgenic models showed hypersynchronized FC before Aβ deposition and hyposynchronized FC at later stages. Early anti-Aβ treatment in TG2576 mice prevented hypersynchronous FC and the associated synaptic impairments and excitatory/inhibitory disbalances.



Hypersynchrony of FC may be used as a new noninvasive read out of early AD and can be recovered by anti-Aβ treatment, encouraging preventive treatment strategies in familial AD.
Bio-Imaging Lab, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Antwerp, Belgium. Electronic address: Disha.Shah@uantwerpen.be.
Disha
D
Shah
Bio-Imaging Lab, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Antwerp, Belgium.
Jelle
J
Praet
Laboratory of Biological Psychology, Department of Psychology, KU Leuven, Leuven, Belgium.
Amira
A
Latif Hernandez
Paul Flechsig Institute for Brain Research, Leipzig, Germany.
Corinna
C
Höfling
Bio-Imaging Lab, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Antwerp, Belgium.
Cynthia
C
Anckaerts
Janssen Prevention Center, San Diego, CA, USA.
Frédérique
F
Bard
Paul Flechsig Institute for Brain Research, Leipzig, Germany.
Markus
M
Morawski
Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
Jan R
JR
Detrez
Department of Biology, University of Antwerp, Antwerp, Belgium.
Els
E
Prinsen
Center of Excellence on Neurodegenerative Diseases, Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
Alessandro
A
Villa
Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium; Cell Systems and Imaging, Department Molecular Biotechnology, University of Ghent, Ghent, Belgium.
Winnok H
WH
De Vos
Center of Excellence on Neurodegenerative Diseases, Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
Adriana
A
Maggi
Laboratory of Biological Psychology, Department of Psychology, KU Leuven, Leuven, Belgium.
Rudi
R
D'Hooge
Laboratory of Biological Psychology, Department of Psychology, KU Leuven, Leuven, Belgium.
Detlef
D
Balschun
Paul Flechsig Institute for Brain Research, Leipzig, Germany.
Steffen
S
Rossner
Bio-Imaging Lab, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Antwerp, Belgium.
Marleen
M
Verhoye
Bio-Imaging Lab, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Antwerp, Belgium.
Annemie
A
Van der Linden
D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D001323:Autoantibodies / Q000494:pharmacology; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology; D003344:Cortical Synchronization / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000517:prevention & control; D062706:Prodromal Symptoms; D012146:Rest
D016229:Amyloid beta-Peptides; D001323:Autoantibodies; D018696:Neuroprotective Agents; D010100:Oxygen
Alzheimer's disease; Amyloidosis; BOLD functional connectivity; Hypersynchrony; PDAPP; Resting-state fMRI; TG2576; Transgenic mouse models