title: Acute amnestic encephalopathy in amyloid-β oligomer-injected mice is due to their widespread diffusion in vivo.
abstract: Amyloid-β (Aβ) oligomers are the suspected culprit as initiators of Alzheimer's disease (AD). However, their diffusion in the brain remains unknown. Here, we studied Aβ oligomers' dissemination and evaluated their in vivo toxicity. Wild-type mice were injected with 50 pmol of synthetic Aβ oligomers (of different size) in the hippocampus. Oligomers diffused largely in the brain as soon as 1 hour and up to 7 days after injection. A transient encephalopathy with memory impairment was induced by this unique injection. The immunoreactivity of the postsynaptic marker PSD95 was diffusely decreased. Similar results (both on memory and PSD95 immunoreactivity) were obtained with delipidated and high molecular weight oligomers (>50 kDa) but not with smaller assemblies. Tau hyperphosphorylation was observed in the oligomer-injected brains. Finally, fos immunostaining was increased in Aβ-derived diffusible ligands-injected mice, suggesting neuronal hyperactivity. Rapid and widespread diffusion of Aβ oligomers was demonstrated in vivo and associated with decreased synaptic markers and memory deficits which gives new insight to the pathogenicity of Aβ.
authors: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Inserm, U 1127, CNRS UMR 7225, ICM, Paris, France; Institut de la mémoire et de la maladie d'Alzheimer, Département de neurologie, Hôpital de la Pitié Salpêtrière, Paris, France. Electronic address: stephane.epelbaum@psl.aphp.fr.
authors: Stéphane
authors: S
authors: Epelbaum
authors: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Inserm, U 1127, CNRS UMR 7225, ICM, Paris, France.
authors: Ihsen
authors: I
authors: Youssef
authors: Department of Neurobiology, Northwestern University, Evanston, IL, USA.
authors: Pascale N
authors: PN
authors: Lacor
authors: Department of Chemistry, Université de Montréal, Montreal, Canada.
authors: Pierre
authors: P
authors: Chaurand
authors: CNRS-UPMC UMR 8256, Biological Adaptation and Ageing (B2A), Université P. et M.Curie, Team: Degenerative Processes in Neurons and Networks (DP2N), Paris, France.
authors: Eric
authors: E
authors: Duplus
authors: CNRS-UPMC UMR 8256, Biological Adaptation and Ageing (B2A), Université P. et M.Curie, Team: Degenerative Processes in Neurons and Networks (DP2N), Paris, France.
authors: Bernard
authors: B
authors: Brugg
authors: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Inserm, U 1127, CNRS UMR 7225, ICM, Paris, France; Laboratoire de neuropathologie Escourolle, Hôpital de la Pitié Salpêtrière, Paris, France.
authors: Charles
authors: C
authors: Duyckaerts
authors: Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Inserm, U 1127, CNRS UMR 7225, ICM, Paris, France.
authors: Benoît
authors: B
authors: Delatour
mesh_terms: D000208:Acute Disease; D000544:Alzheimer Disease / Q000209:etiology; D000647:Amnesia / Q000139:chemically induced* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D001692:Biological Transport; D001704:Biopolymers; D001921:Brain / Q000378:metabolism; D001927:Brain Diseases / Q000139:chemically induced* / Q000378:metabolism; D004058:Diffusion; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus; D007267:Injections; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D010766:Phosphorylation; D013569:Synapses / Q000187:drug effects; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D001704:Biopolymers; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D016875:tau Proteins; D051528:Guanylate Kinases
keywords: Alzheimer's disease; Amyloid β; In vivo animal model; Neurotoxicity; Oligomers