P3–428: Stability of nicotinic acetylcholine receptor binding in the frontal and temporal cortex of subjects with mild cognitive impairment

null mutant mice and slices treated with anti-RAGE antibodies. Results: Abeta(1-42) at 200 nM was able to inhibit the expression of LTP after tetanic stimulation without affecting basal synaptic transmission. Remarkably, different concentrations of Abeta (1-42) were not able to inhibit LTP in slices from RAGE null mutant mice or in slices treated with blocking antibodies against RAGE. To test the hypothesis that RAGE-Abeta interaction could lead to LTP impairment trough activation of MAP-kinases, experiments were repeated in the presence of specific inhibitors. In particular, SB203580 (1microM), an inhibitor of p38 MAP-kinase, was found to rescue LTP in Abeta (1-42) treated slices. Cell culture experiments confirmed that Abeta (1-42) modulates p38 phosphorylation at [pTpY180/182] in cortical neurons. Moreover, treatment with anti-RAGE antibodies prevented changes of p38 phosphorylation by Abeta (1-42). Conclusions: Our results indicate that non-neurotoxic concentrations of Abeta (1-42) impair LTP in mouse neocortex through RAGE mediated activation of p38 MAP kinase. (Supported by NIA and Fondazione CariPisa, 05/140).