## 2 Results
Both \(A\beta\)PP-wt and Swedish mutation \(A\beta\)PP-sw genes affected UBOH-dependent effects on viable cells in comparison to empty-vector transfected cells. The results amounted to: \(p<0.0001\) for interaction, \(p=0.0004\) for genes, \(p<0.0001\) for UBOH. (**E**) Adding FOH rescued ATR, or SIM, or M\(\beta\)CD diminished viable cells. Both \(A\beta\)PP-wt and Swedish mutation \(A\beta\)PP-sw genes affected UBOH-dependent effects on viable cells in comparison to empty-vector transfected cells. The results amounted to: \(p<0.0001\) for interaction, \(p<0.0001\) for FOH. (**F**) Adding GGOH rescued ATR, or SIM, or M\(\beta\)CD diminished viable cells. Both \(A\beta\)PP-wt and Swedish mutation \(A\beta\)PP-sw genes affected GGOH-dependent effects on viable cells in comparison to empty-vector transfected cells. The results amounted to: \(p=0.0004\) for interaction, \(p<0.0001\) for genes, \(p<0.0001\) for GGOH; Error bars = S.E.M., and \({}^{*}p<0.05\), \({}^{**}p<0.01\), \({}^{***}p<0.001\) for comparison with non-treated control cells. The results are indicative of three independent experiments performed in eight replicates. Effects of Non-Sterol Isoprenoids (MEV, DOH, UBOH, FOH, GGOH) vs. CHOL-PEG on \(\beta\)-Amyloid (A\(\beta\)1-40) Secretion by Neuronal PC-12 Cells Affected by MEV Pathway Modulators Status or Cholesterol Chelator Methyl-\(\beta\)Cyclodextrin (M\(\beta\)CD) in PC-12 Cells Overexpression A\(\beta\)PP-wt or A\(\beta\)PP-sw Gene  
The average concentrations of amyloid (A\(\beta\)1-40) in supernatants collected from treatments shown on Figure 2 points to fairly low amyloidogenic A\(\beta\)PP processing in neuronal PC-12 cells upon statins (ATR, SIM, 50 \(\upmu\)M) or M\(\beta\)CD (0.2 mM) treatments (Figure 3A). The A\(\beta\) production increased after additional co-treatment with MEV, DOH or UBOH (Figure 3B-D), but it returned to control levels after co-treatment with FOH, GGOH or Chol-PEG (Figure 3E-G). These data point to the central role played by protein prenylation and cholesterol itself in controlling the activity of amyloidogenic A\(\beta\)PP processing. Cellular media were harvested and assayed for the presence of A\(\beta_{40}\) normalized for cell viability, as determined with the MTT assay. Experiments were performed at least three times, and each point in each experiment has eight repetitions. Figure 3: Cont. Effects of Mevalonate (MEV, FOH, GGOH) or Water-Soluble Cholesterol (Chol-PEG) on Selected Protein Expression Levels in Cells Affected by MEV Pathway Modulators (Atorvastatin - ATR, Simvastatin - SIM)  
As neuronal cells are most likely targeted by statins rather than M\(\beta\)CD, we sought the impact of ATR or SIM (50 \(\upmu\)M each), as well as co-treatment with selected non-sterol isoprenoids, on A\(\beta\)PP amyloidogenic processing. First, amyloidogenic A\(\beta\)PP processing was observed ultimately in _A\(\beta\)PP_-sw-, whereas non-amyloidogenic A\(\beta\)PP cleavage was found exclusively in neuronal cells bearing _A\(\beta\)PP_-wt (Figure 4A,B). Co-treatment with non-sterol isoprenoids GGOH (10 \(\upmu\)M), FOH (10 \(\upmu\)M), MEV (100 \(\upmu\)M) and Chol-PEG (1 mM) in non-toxic concentrations strongly stimulated (\(p<0.05\)) clusterin protein levels in PC-12 neuronal cells. The effects of co-treatment with non-sterol isoprenoids, but not Chol-PEG, were more profound in empty-vector than in _A\(\beta\)PP_-wt and _A\(\beta\)PP_-sw transfected cells, showing the high importance of protein prenylation in neuronal cells. Figure 4: _Cont._  
Figure 3: Effect of mevalonate (MEV, 100 \(\upmu\)M), dolichol (DOH, 0.1 \(\upmu\)g/mL), ubiquinol (UBOH, 10 \(\upmu\)g/mL), farresol (FOH, 10 \(\upmu\)M), geranylgeraniol (GGOH, 10 \(\upmu\)M) or water soluble cholesterol (Chol-PEG, 1 mM) on amyloid-\(\beta\) (A\(\beta_{40}\)) secretion by neural PC-12 cells affected by MEV pathway modulators (atorvastatin – ATR, simvastatin – SIM, 50 \(\upmu\)M each) or cholesterol chelator methyl-\(\beta\)-cyclodextrintrin (M\(\beta\)CD, 0.2 mM).