## 1 Introduction
Whether sCLU protein assists in the \"nonprofessional\" phagocytosis mediated by epithelial, endothelial, fibroblast and smooth muscle cells is a matter of debate, even though sCLU has the ability to bind a broad spectrum of proteins playing the role of the docking platform for cellular uptake [20]. sCLU may also play a role in transport/uptake vehicle of amyloid beta (A\(\beta\)) in AD [12; 13]. Several cohort studies and meta-analyses suggest that _CLU_ gene rs11136000 variant is significantly associated with Alzheimer's disease [21; 22; 23]. Numerous papers report higher clusterin expression in the brains affected by AD [24; 25; 26]. It colocalizes with A\(\beta\), the product of subsequent A\(\beta\)PP processing by \(\beta\)- (BACE1) and \(\gamma\)-secretase, suggesting the central role played by this protein in senile plaque formation [9; 26; 27]. sCLU was shown to inhibit the aggregation [28] while promoting evacuation of A\(\beta\) through the blood brain barrier (BBB) [25; 29]. The latter event most likely occurs through CLU A\(\beta_{42}\)-induced endocytosis and accumulation in astrocytes [30; 31]. Furthermore, _CLU rs1136000_single nucleotide polymorphism (SNP) modified the cerebrospinal fluid (CSF) levels of the microtubule-associated protein Tau in AD patients [32]. Furthermore, intracellular clusterin (iCLU)was upregulated in the brain of Tau overexpressing Tg4510 mice. There are some reports pointing to oxidative stress induced by sCLU-A\(\beta\) complexes [27; 28], while others emphasize binding of A\(\beta\) as the indirect cytoprotective mechanism of A\(\beta\) clearance and transport [33; 34]. Importantly, clusterin protein concentration paralleled mRNA expression, and this protein was suggested to be a good marker of cell senescence [35; 36]. Physiological mechanisms of A\(\beta\) clearance are controlled on one hand by extracellular degradation through neprilysin and insulin-degrading enzymes, on the other hand by astrocytes and microglia via endocytotic/phagocytotic pathways [37; 38]. A\(\beta\) clearance from brain to blood by transcytosis across the BBB is possible only if the peptide is bound to apolipoprotein E (apoE), \(\alpha\)2-macroglobulin (\(\alpha\)2M) or sCLU. The latter (1:1 sCLU-A\(\beta\) complex binds to lipoprotein low density-receptor-related protein 2 (LRP-2/megalin receptor) expressed in endothelium, ependyma and choroid plexus, whereas the apoE-A\(\beta\) and \(\alpha\)2M-A\(\beta\) complexes need LRP-1 [12; 39]. The opposite, A\(\beta\) transport from blood to brain via BBB, is mediated by receptors for advanced glycation end products (RAGE), thereby highlighting the importance of respective receptor balance in A\(\beta\) brain deposition. As demonstrated by others, sCLU might play important role in the endocytosis/autophagy as astrocytes loaded with fibrillar A\(\beta\) had upregulated sCLU expression levels [30]. Cells are induced to form cytoplasmic vacuoles, presumably due to uptake of sCLU-A\(\beta\) complexes, pointing to sCLU as critical extracellular component regulating A\(\beta\) clearance from the brain. Previously, we showed that PC-12 neuronal cells with _A\(\beta\)PP_-sw (Swedish mutation) but not that of _A\(\beta\)PP_-wt gene or empty vector had enhanced representation of autophagy-like vacuoles [40]. In the present study we investigated whether increased A\(\beta\) production in _A\(\beta\)PP_-sw expressing PC-12 neuronal cells is paralleled by enhanced expression of sCLU. Additionally, we wished to know how A\(\beta\) processing in _A\(\beta\)PP_-sw expressing cells affects cell viability. To examine this in the context of how important the MEV pathway is, we tested several intermediates including non-sterol isoprenoids and water-soluble cholesterol, to see whether any of the substance can prevent neuronal cells from atorvastatin- or simvastatin-induced fall in cell viability. We also tested the effect of selective inhibitors of MEV pathway enzymes on viability measurement of neuronal cells.