The interaction of AChE with PrP fibrils inhibits AChE enzymatic activity and enhances the cytotoxicity of both monomeric alpha-helix-rich and amyloid fibril PrP conformers in primary neurons. a PrP fibrils inhibit AChE enzymatic activity. Left panel: 7.3 nM AChE was pre-incubated for different periods of time without (open circles) or with 25 μm of monomeric (open squares) or fibrillar PrP (black circles) before initiation of the reaction with ACh. Right panel: Decrease in the observed AChE activity as a function of PrP fibril concentration. b Neurons were cultured for 2 days and then incubated with monomeric (PrP) or fibrillar (Fib) PrP isoforms (final concentration, 1 μM), 0.5 μM AChE or the PrP-AChE mix. Neuronal cell death was quantified and expressed as the percentage relative to the value of control cells (vehicle). Each set of data is the mean value ± S.D. (in percentage) of four experiments; five independent microscopic fields were counted for each experiment. **P < 0.005, one-way ANOVA. The Tukey test was used for post-hoc comparison after ANOVA.