Amyloid beta protein dimer-containing human CSF disrupts synaptic plasticity: prevention by systemic passive immunization.
Item Type:Journal Article
Citation:Klyubin I, Betts V, Welzel AT, Blennow K, Zetterberg H, Wallin A, Lemere CA, Cullen WK, Peng Y, Wisniewski T, Selkoe DJ, Anwyl R, Walsh DM, Rowan MJ, Amyloid beta protein dimer-containing human CSF disrupts synaptic plasticity: prevention by systemic passive immunization., The Journal of Neuroscience, 28, 16, 2008, 4231-7
Amyloid beta protein dimer-containing human CSF disrupts synaptic plasticity - prevention by systemic passive immunization.pdf (Published (publisher's copy) - Peer Reviewed) 623.3Kb
Supplemental_Figure_1_-_Klyubin.gif (GIF image) 84.59Kb
Supplemental_Figure_2_-_Klyubin.gif (GIF image) 86.69Kb
Supplemental_Figure_3_-_Klyubin.gif (GIF image) 25.01Kb
The current development of immunotherapy for Alzheimer's disease is based on the assumption that human-derived amyloid beta protein (Abeta) can be targeted in a similar manner to animal cell-derived or synthetic Abeta. Because the structure of Abeta depends on its source and the presence of cofactors, it is of great interest to determine whether human-derived oligomeric Abeta species impair brain function and, if so, whether or not their disruptive effects can be prevented using antibodies. We report that untreated ex vivo human CSF that contains Abeta dimers rapidly inhibits hippocampal long-term potentiation in vivo and that acute systemic infusion of an anti-Abeta monoclonal antibody can prevent this disruption of synaptic plasticity. Abeta monomer isolated from human CSF did not affect long-term potentiation. These results strongly support a strategy of passive immunization against soluble Abeta oligomers in early Alzheimer's disease.
Science Foundation Ireland (SFI)
Type of material:Journal Article
Series/Report no:The Journal of Neuroscience
Availability:Full text available