## 1 Introduction  
Cholesterol synthesis and non-sterol isoprenoids play a vital role during the development of the central nervous system (CNS) [1, 2]. Cholesterolis in the brain is fully autonomous because the blood brain barrier (BBB) obstructs plasma lipoproteins from entry into the cerebrospinal fluid (CSF). Interestingly, unesterified cholesterol is found mainly in myelin sheets and the plasma membrane of both neurons and glia, although the latter are the chief neuron suppliers. In the adult brain there is dynamic exchange of cholesterol complexed to apolipoprotein E between astrocytes (donors) and neurons (acceptors) [3]. The bulk of the evidence, however, suggests that isoprenoids rather than cholesterol itself play a crucial role in the adult brain [4; 5]. Isoprenoids are synthesized in the mevalonate (MEV) pathway alternatively/together with cholesterol whereby 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR, E.C 1.1.1.34) is a step limiting enzyme, ubiquitously expressed in animal cells, and hampered by a group of hypercholesterolemia lowering drugs named statins. statins have access to the brain either through their lipophilicity or active transport [6]. Isoprenoid synthesis starts with five carbon chain (5-C) isoprene formed from decarboxylation of mevalonate pyrophosphate (MEVPP) to form isopentenyl pyrophosphate (IPP)/dimethylallyl diphosphate (DMPP). This step is followed by several condensations of IPP/DMPP or other isoprenoids resulted in geranyl pyrophosphate (GPP, 10-C), farnesyl pyrophosphate (FPP, 15-C) or geranylgeranyl pyrophosphate (GGPP, C-20). FPP is at the branching point to cholesterol synthesis, where together with another FPP molecule it rises to squalene (C-30). Compared to other tissues, FPP and GPP levels are highest in the brain [7]. Taken together, statins inhibit the MEV pathway, which plays a pivotal role in de novo cholesterol and isoprenoid synthesis. It is a matter of debate which end-product of the MEV pathway and in what circumstances are vital for brain functions in health and disease. With regard to Alzheimer's disease (AD) overexpressed amyloid beta precursor protein (A\(\beta\)PP), a substrate for amyloid beta (A\(\beta\)) synthesis, was reported to suppress HMGCR [8]. Clusterin, also known as Apolipoprotein J, the glycoprotein secreted (sCLU) mainly by neurons and glia, is widely recognized as extracellular chaperone with multifunctional properties including cell aggregation and inhibition of membrane attack complex in complement cascade [9]. Clusterin expression levels are higher in the brain in comparison to many other tissues [10; 11]. sCLU occupies an original role in AD as it is involved in oxidative stress, inflammatory response and clearance of A\(\beta\) from brain [12; 13]. Moreover, sCLU is believed to suppress immune reaction, as it is induced through toll like receptor (TLR3) signaling to inhibit nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), the transcription factor controlling key functions of immune cells [14]. There are other proofs that sCLU is involved in immune tolerance, as it was demonstrated to limit myocarditis [15] and trouble-free removal of dead cells and cell debris [16]. Clusterin (_CLU_) gene expression is observed in damaged tissue and it is unevenly distributed with some grey matter areas of higher representation in the rat brain [17]. _CLU_ mRNA is induced by an at present unknown signaling pathway through plasma membrane phospholipid phosphatidylinositol (PS), playing a major role as a marker of apoptotic and necrotic cells [16]. The role of CLU in neuroprotection is apparently equivocal [18]. Anyway, experimental data show sCLU seems to fulfill the role of extracellular chaperone by promoting the disposal of dead cells and cell remnants [19].