Amyloid β protein dimer-containing human CSF disrupts synaptic plasticity:: Prevention by systemic passive immunization

被引：268

作者：

Klyubin, Igor ^{[1
,2
]}

Betts, Vicki ^{[4
]}

Welzel, Alfred T. ^{[4
]}

Blennow, Kaj ^{[5
]}

Zetterberg, Henrik ^{[5
]}

Wallin, Anders ^{[5
]}

Lemere, Cynthia A. ^{[6
,7
]}

Cullen, William K. ^{[1
,2
]}

Peng, Ying ^{[6
,7
]}

Wisniewski, Thomas ^{[8
]}

Selkoe, Dennis J. ^{[6
,7
]}

Anwyl, Roger ^{[2
,3
]}

Walsh, Dominic M. ^{[4
]}

Rowan, Michael J. ^{[1
,2
]}

机构：

[1] Trinity Coll Dublin, Dept Pharmacol & Therapeut, Dublin 2, Ireland

[2] Trinity Coll Dublin, Inst Neurosci, Dublin 2, Ireland

[3] Trinity Coll Dublin, Dept Physiol, Dublin 2, Ireland

[4] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 4, Ireland

[5] Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, SE-40530 Gothenburg, Sweden

[6] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA

[8] NYU, Sch Med, Dept Neurol, New York, NY 10016 USA

来源：

JOURNAL OF NEUROSCIENCE | 2008年 / 28卷 / 16期

基金：

英国惠康基金;

关键词：

synaptic plasticity; amyloid beta protein; Alzheimer's disease; LTP; long-term potentiation; CSF; hippocampus;

D O I：

10.1523/JNEUROSCI.5161-07.2008

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The current development of immunotherapy for Alzheimer's disease is based on the assumption that human-derived amyloid beta protein ( A beta) can be targeted in a similar manner to animal cell-derived or synthetic A beta. Because the structure of A beta depends on its source and the presence of cofactors, it is of great interest to determine whether human-derived oligomeric A beta 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 A beta dimers rapidly inhibits hippocampal long-term potentiation in vivo and that acute systemic infusion of an anti-A beta monoclonal antibody can prevent this disruption of synaptic plasticity. A beta monomer isolated from human CSF did not affect long-term potentiation. These results strongly support a strategy of passive immunization against soluble A beta oligomers in early Alzheimer's disease.

引用

页码：4231 / 4237

页数：7

共 33 条

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