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The Journal of Neuroscience, April 16, 2008, 28(16):4231-4237; doi:10.1523/JNEUROSCI.5161-07.2008

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Neurobiology of Disease
Amyloid β Protein Dimer-Containing Human CSF Disrupts Synaptic Plasticity: Prevention by Systemic Passive Immunization

Igor Klyubin,^1,2 Vicki Betts,⁴ Alfred T. Welzel,⁴ Kaj Blennow,⁵ Henrik Zetterberg,⁵ Anders Wallin,⁵ Cynthia A. Lemere,⁶ William K. Cullen,^1,2 Ying Peng,⁶ Thomas Wisniewski,⁷ Dennis J. Selkoe,⁶ Roger Anwyl,^1,3 Dominic M. Walsh,⁴ and Michael J. Rowan^1,2

¹Institute of Neuroscience and Departments of ²Pharmacology and Therapeutics and ³Physiology, Trinity College, Dublin 2, Ireland, ⁴Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland, ⁵Institute of Neuroscience and Physiology, Department of Neurochemistry and Psychiatry, Sahlgrenska Academy at Göteborg University, SE-405 30 Göteborg, Sweden, ⁶Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts 02115, and ⁷Department of Neurology, New York University School of Medicine, New York, New York 10016

Correspondence should be addressed to Michael J. Rowan, Department of Pharmacology and Therapeutics, Biotechnology Building, Trinity College, Dublin 2, Ireland. Email: mrowan{at}tcd.ie

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

Key words: synaptic plasticity; amyloid β protein; Alzheimer's disease; LTP; long-term potentiation; CSF; hippocampus

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Received Aug. 16, 2007; revised March 11, 2008; accepted March 12, 2008.

Correspondence should be addressed to Michael J. Rowan, Department of Pharmacology and Therapeutics, Biotechnology Building, Trinity College, Dublin 2, Ireland. Email: mrowan{at}tcd.ie

This article has been cited by other articles:

				N.-W. Hu, I. M. Smith, D. M. Walsh, and M. J. Rowan Soluble amyloid-{beta} peptides potently disrupt hippocampal synaptic plasticity in the absence of cerebrovascular dysfunction in vivo Brain, September 1, 2008; 131(9): 2414 - 2424. [Abstract] [Full Text] [PDF]

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