Acute amnestic encephalopathy in amyloid-beta oligomer-injected mice is due to their widespread diffusion in vivo

作者：Epelbaum Stephane^*; Youssef Ihsen; Lacor Pascale N; Chaurand Pierre; Duplus Eric; Brugg Bernard; Duyckaerts Charles; Delatour Benoit

来源：Neurobiology of Aging, 2015, 36(6): 2043-2052.

DOI：10.1016/j.neurobiolaging.2015.03.005

• Alzheimer's disease
• Amyloid beta
• Oligomers
• In vivo animal model
• Neurotoxicity

Amyloid-beta (A beta) oligomers are the suspected culprit as initiators of Alzheimer's disease (AD). However, their diffusion in the brain remains unknown. Here, we studied A beta oligomers' dissemination and evaluated their in vivo toxicity. Wild-type mice were injected with 50 pmol of synthetic A beta 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 A beta-derived diffusible ligandseinjected mice, suggesting neuronal hyperactivity. Rapid and widespread diffusion of Ab oligomers was demonstrated in vivo and associated with decreased synaptic markers and memory deficits which gives new insight to the pathogenicity of A beta.

• 出版日期2015-6
• 单位西北大学