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P1‐169: Roasting products of coffee (melanoidins) and their associations with Alzheimer's disease
Author(s) -
Sauer Tanja,
Pischetsrieder Monika,
Muench Gerald
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.719
Subject(s) - roasting , hydrogen peroxide , catalase , antioxidant , ribose , chemistry , oxidative stress , lysine , food science , biochemistry , nf κb , enzyme , signal transduction , amino acid
Background: The inability to form new memories is an early clinical sign of Alzheimer’s disease (AD) and the Ab peptide seems to play a key role in this process. Soluble, bio-derived oligomers of Ab are proposed as key mediators of synaptic and cognitive dysfunction. We investigated the effect of synthetic Ab1-42 oligomers on memory consolidation and retrieval in mice tested in the novel object recognition task; the ability of an anti-Ab antibody to prevent their detrimental action and if the deficit was reversible. Because recent data showed an involvement of PrP in mediating oligomer action, we investigated their physical interaction and whether Ab oligomers would affect memory of PrP knock-out (Prnp) mice. Methods: Following intracerebroventricle injection of either Ab1-42 monomer, oligomers or fibrils (1.0 mM), mice underwent the object familiarization phase (day 1) and the memory test phase (day 2). Memory abilities were determined calculating the discrimination index based on the exploration time on either the novel or familiar object. To determine whether oligomers affect memory consolidation or retrieval one single injection was made either before familiarization or memory evaluation. The involvement of PrP was determined injecting Ab oligomers in Prnp mice, whereas the interaction between Ab oligomers and PrP was verified using the surface plasmon resonance technique (SPR). Results: Our findings show that Ab1-42 oligomers impaired consolidation of long-term recognition memory, whereas mature Ab1-42 fibrils and freshly dissolved peptide did not. Similar results were obtained injecting Ab 1-40 oligomers. Retrieval of properly stored memories was not affected. The deficit induced by the oligomers was prevented by an anti-Ab antibody and fully recovered 10 days after the injection. We confirmed by SPR that Ab1-42 oligomers interact with PrP, with nanomolar affinity, however PrP-expressing and Prnp mice were equally susceptible to the cognitive deficits induced by Ab oligomer injection. Conclusions: Our data show that Ab oligomers are responsible for the induction of a reversible memory impairment by blocking memory consolidation. An Ab antibody can prevent such effects. Although we confirmed a binding between Ab oligomers and PrP, our data suggest that PrP is not required for their in vivo detrimental effects.