Clusterin (CLU; also known as apolipoprotein J, ApoJ) is a protein of inconstant structure known to be involved in diverse processes inside and outside of brain cells. CLU can act as a protein chaperon or protein solubilizer, lipid transporter as well as redox sensor and be anti- or proapoptotic, depending on context. Primary structure of CLU is encoded by CLU gene which contains single nucleotide polymorphisms (SNP's) associated with the risk of late-onset Alzheimer's disease (LOAD). Studying a sample of Czech population and using the case-control association approach we identified C allele of the SNP rs11136000 as conferring a reduced risk of LOAD, more so in females than in males. Additionally, data from two smaller subsets of the population sample suggested a possible association of rs11136000 with diabetes mellitus. In a parallel study, we found no association between rs11136000 and mild cognitive impairment (MCI). Our findings on rs11136000 and LOAD contradict those of some previous studies done elsewhere. We discuss the multiple roles of CLU in a broad range of molecular mechanisms that may contribute to the variability of genetic studies of CLU in various ethnic groups. The above discordance notwithstanding, our conclusions support the association of rs1113600 with the risk of LOAD.

Bosch Institute and Discipline of Anatomy and Histology School of Medical Sciences Faculty of Medicine and Health The University of Sydney Sydney NSW 2006 Australia

Department of Epidemiology and Public Health Faculty of Medicine University of Ostrava Ostrava Czech Republic

Laboratory of Neurobiology and Molecular Psychiatry Department of Biochemistry Faculty of Science Masaryk University Kamenice 5 625 00 Brno Czech Republic

Laboratory of Neurobiology and Pathological Physiology Institute of Animal Physiology and Genetics Academy of Sciences of the Czech Republic Veveří 97 602 00 Brno Czech Republic

Present address Faculty of Health Sciences Palacký University Olomouc Olomouc Czech Republic

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Six genetically linked mutations in the CD36 gene significantly delay the onset of Alzheimer's disease