Synthetic amyloid-beta oligomers impair long-term memory independently of cellular prion protein.

Abstract

Inability to form new memories is an early clinical sign of Alzheimer's disease (AD). There is ample evidence that the amyloid-beta (Abeta) peptide plays a key role in the pathogenesis of this disorder. Soluble, bio-derived oligomers of Abeta are proposed as the key mediators of synaptic and cognitive dysfunction, but more tractable models of Abeta-mediated cognitive impairment are needed. Here we report that, in mice, acute intracerebroventricular injections of synthetic Abeta(1-42) oligomers impaired consolidation of the long-term recognition memory, whereas mature Abeta(1-42) fibrils and freshly dissolved peptide did not. The deficit induced by oligomers was reversible and was prevented by an anti-Abeta antibody. It has been suggested that the cellular prion protein (PrP(C)) mediates the impairment of synaptic plasticity induced by Abeta. We confirmed that Abeta(1-42) oligomers interact with PrP(C), with nanomolar affinity. However, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment. These data suggest that Abeta(1-42) oligomers are responsible for cognitive impairment in AD and that PrP(C) is not required.

• Authors: Claudia Balducci, Marten Beeg, Matteo Stravalaci, Antonio Bastone, Alessandra Sclip, Emiliano Biasini, Laura Tapella, Laura Colombo, Claudia Manzoni, Tiziana Borsello, Roberto Chiesa, Marco Gobbi, Mario Salmona, Gianluigi Forloni
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 107 Issue 5 Pg. 2295-300 (Feb 02 2010) ISSN: 1091-6490 [Electronic] United States
• PMID: 20133875 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Peptide Fragments
• PrPC Proteins
• Prion Proteins
• Prions
• Prnp protein, mouse
• amyloid beta-protein (1-42)

Topics

• Alzheimer Disease (etiology)
• Amyloid beta-Peptides (chemical synthesis, chemistry, pharmacology)
• Animals
• Cognition Disorders (etiology, metabolism)
• Humans
• Injections, Intraventricular
• Male
• Memory (drug effects, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neuronal Plasticity (drug effects, physiology)
• Peptide Fragments (chemical synthesis, chemistry, pharmacology)
• PrPC Proteins (metabolism)
• Prion Proteins
• Prions (genetics, metabolism)
• Protein Binding
• Surface Plasmon Resonance