Amyloid beta protein dimer-containing human CSF disrupts synaptic plasticity: prevention by systemic passive immunization.

• 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.

Keyword

Alzheimer Disease

immunology

metabolism

therapy

Amyloid beta-Protein

administration & dosage

cerebrospinal fluid

immunology

Animals

Antibodies

Monoclonal

administration & dosage

CHO Cells

Cricetinae

Cricetulus

Dimerization

Humans

Immunization

Passive

methods

Long-Term Potentiation

immunology

Male

Neuronal Plasticity

immunology

Rats

Rats

Wistar

Synapses

immunology

Publication and Content Type

ref (subject category)

art (subject category)