Alzheimer disease (AD) is a neurodegenerative disease that is estimated to affect 15 millions people worldwide. The main cause of AD is generally attributed to the accumulation of b-amyloid (Ab) protein in typical plaques. Recently, the N-acetyl-glucosamine polymer "Chitin" has also been found within Ab plaques (Castellani et al. 2005), but its potential role in the pathogenesis of AD remains to be elucidated. We found that Chitin or high concentrations of its precursors (N-acetyl-glucosamine+UDP) have a specific neurotoxic effect, reducing to 40% the survival of hippocampal cultured neurons after 48hrs in vitro, while leaving fibroblasts unperturbed. The neurotoxic effect was further replicated in hippocampal slice cultures. Functionally, the acute application of Chitin's precursors to hippocampal slices of adult mice, prevents the expression of Long Term Potentiation of CA3 to CA1 glutamatergic synapses (excitatory post synaptic field potential slope relative to baseline: control 70%, n=8; with Chitin's precursors 17%, n=7). These data support the hypothesis that Chitin accumulation during AD may induce structural and functional deficits that may contribute to Ab-derived neurotoxicity.