The C risk allele at rs11136000 is associated with lower CLU expression (Allen et al., 2012; Ling et al., 2012), reflecting decreased soluble, secreted clusterin protein throughout life (Ling et al., 2012). (2011). J. Biochem. Exp. Ling et al. 270, 13070–13075. (2012). Effects of clusterin over-expression on metastatic progression and therapy in breast cancer. Mol. (2015). To date, rs11136000 is the most studied SNP found in CLU and although it was once considered to be the most influential CLU SNP affecting AD risk in Caucasian populations, it is now ranked as the second, after rs9331896. doi: 10.1016/j.yexcr.2005.06.012, Kapron, J. T., Hilliard, G. M., Lakins, J. N., Tenniswood, M. P., West, K. A., Carr, S. A., et al. doi: 10.1111/cas.12088, Yang, C. R., Leskov, K., Hosley-Eberlein, K., Criswell, T., Pink, J. J., Kinsella, T. J., et al. doi: 10.1158/1541-7786.MCR-11-0379, Shuai, P., Liu, Y., Lu, W., Liu, Q., Li, T., and Gong, B. Segmentations were assessed visually for defects from multiple views. This figure was produced using icons in the icon library of the Reactome database that are free for download and modification: (https://reactome.org/icon-lib) Accessed August 28, 2018; (Sidiropoulos et al., 2017). In contrast, there is some indication that intracellular clusterin may promote apoptosis. Rs11136000 was considered to be the main CLU SNP that altered AD risk (Harold et al., 2009; Lambert et al., 2009). Int. U.S.A. 114, E6962–E6971. doi: 10.1189/jlb.0310157, Squitti, R., Polimanti, R., Bucossi, S., Ventriglia, M., Mariani, S., Manfellotto, D., et al. Bettens K, Brouwers N, Engelborghs S, Lambert JC, Rogaeva E, Vandenberghe R, Le Bastard N, Pasquier F, Vermeulen S, Van Dongen J, Mattheijssens M, Peeters K, Mayeux R, St George-Hyslop P, Amouyel P, De Deyn PP, Sleegers K, Van Broeckhoven C. Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk. doi: 10.1167/iovs.09-3774, Kim, N., Yoo, J. C., Han, J. Y., Hwang, E. M., Kim, Y. S., Jeong, E. Y., et al. Endocytosis is required for synaptic activity-dependent release of amyloid-β in vivo. ER stress resulted in the cytoplasmic accumulation of clusterin in a Drosophila model of amyotrophic lateral sclerosis (ALS), reducing accumulation of TDP-43 protein inclusions and partially rescuing the ALS-like phenotype (Gregory et al., 2017). Brain Res. We found no significant genotype by diagnosis interaction in these analyses (p = 0.629 and p = 0.900 for rs11136000; p = 0.562 and p = 0.842 for rs1532278, at 1- and 2-year follow-ups, respectively). CLU is transcribed into the mRNA NM_001831.3, containing exons 1–9. As previously discussed, SNPs within CLU have been shown to interact with each other to influence hippocampal volume (Roussotte et al., 2014), but relationships among different AD GWAS genes and their SNPs are mostly unexplored. Zhou Y, Wang J, Wang K, Li S, Song X, Ye Y, Wang L, Ying B. As the volume images were already normalized for overall brain size by the nine-parameter affine alignment, additional volume normalization was unnecessary in these analyses. In seminal work by DeMattos et al. Chem. After 1 year, carrying two C alleles was associated with greater overall ventricular expansion (p = 0.003, F-ratio = 9.135 for rs11136000, Table 3; p = 0.002, F-ratio = 9.313 for rs1532278, Table 4), after controlling for sex, age, and dementia status. 94, 43–52. Lambert et al. (2015). Interaction between Aβ and redox metal ions is also observed; Cu2+ and Aβ produce H2O2 (Huang et al., 1999; Cuajungco et al., 2000; Opazo et al., 2002) and Aβ toxicity is enhanced in the presence of Cu2+ (Opazo et al., 2002). Apolipoprotein J and Alzheimer’s amyloid beta solubility. Keyword: GWAS and other large-scale association studies: Note to users: the redesign of the AlzGene database code has been completed (please visit our sister databases at www.pdgene.org and www.alsgene.org).We are aiming to include GWAS meta-analysis results published in 2013 by the International Genomics of Alzheimer’s Project (IGAP) consortium. CLU expression appears highly influenced by epigenetic factors in retinal pigment epithelial cells where valproic acid, a histone deacetylase (HDAC) inhibitor, induces a significant increase in clusterin protein expression and secretion (Suuronen et al., 2007). A., Berg, S., et al. The growing tool box of gene editing tools, the availability of iPSCs from well characterized patient backgrounds, and increased sophistication in building molecular networks from multi-modal ‘omics’ data will all accelerate this search. Neurosci. In fact, in a meta-analysis of three large cohorts of AD patients and control subjects, high-density SNP mapping around this locus mapped the association signal to a more 5′ CLU region (Bettens et al., 2012). Inhibition of NF-kappaB-dependent Bcl-xL expression by clusterin promotes albumin-induced tubular cell apoptosis. There are two major types of Alzheimer’s disease, early onset and the more common late onset. Within the Golgi, cleavage between residues 227 and 228 results in the formation of the α- and β-chains linked by five disulphide bonds (Urban et al., 1987; Wong et al., 1993; Kapron et al., 1997; Yang et al., 2000). 116, 3109–3121. Genet. 48, 718–728. Overexpression of apolipoprotein J in human fibroblasts protects against cytotoxicity and premature senescence induced by ethanol and tert-butylhydroperoxide. Complement activation in multiple sclerosis plaques: an immunohistochemical analysis. J. Alzheimers Dis. 148, 1971–1983. CLU mRNA was first observed to increase in the rat ventral prostate after castration, an observation initially attributed to androgen repression but is now thought to be due to castration-induced apoptosis (Montpetit et al., 1986; Leger et al., 1987). Cerebrovascular effects of apolipoprotein E: implications for Alzheimer disease. Biochem. 368, 117–127. TREM2 binds to apolipoproteins, including APOE and CLU/APOJ, and thereby facilitates uptake of amyloid-beta by microglia. doi: 10.1016/0896-6273(90)90342-D, May, P. C., Robison, P., Fuson, K., Smalstig, B., Stephenson, D., and Clemens, J. Correlation of rs9331888 polymorphism with Alzheimer’s disease among Caucasian and Chinese populations: a meta-analysis and systematic review. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. A. EZH2 mediates epigenetic silencing of neuroblastoma suppressor genes CASZ1, CLU, RUNX3 and NGFR. These associations remained significant at the 2-year follow-up (p = 0.020, F-ratio = 5.470 for rs11136000, Table 3; p = 0.032, F-ratio = 4.632 for rs1532278, Table 4). doi: 10.1379/1466-1268(2002)007<0023:OOAJIH>2.0.CO;2, Dunckley, T., Beach, T. G., Ramsey, K. E., Grover, A., Mastroeni, D., Walker, D. G., et al. doi: 10.1074/jbc.274.11.6875, Imhof, A., Charnay, Y., Vallet, P. G., Aronow, B., Kovari, E., French, L. E., et al. doi: 10.1126/science.1099320, Greenough, M. A., Ramírez Munoz, A., Bush, A. I., and Opazo, C. M. (2016). Science 261, 921–923. doi: 10.1016/j.jmb.2005.05.046, Poon, S., Easterbrook-Smith, S. B., Rybchyn, M. S., Carver, J. Commun. aParticipants coded as “0” carried two risk alleles at both loci, subjects coded as “1” carried at least one protective allele at either locus, individuals coded as “2” carried at least one protective allele at both loci. The surface models described in Segmentation of the lateral ventricles, above were used. MCI patients show increased plasma clusterin in the presence of rs11136000-C allele, which negatively correlates with cognitive function scores (Cai et al., 2016). 40, 930–934. Rep. 8:1906. doi: 10.1038/s41598-018-20316-1, Pietersen, C. Y., Mauney, S. A., Kim, S. S., Lim, M. P., Rooney, R. J., Goldstein, J. M., et al. 7, 338–343. Multiple amphiphysin II splice variants display differential clathrin binding: identification of two distinct clathrin-binding sites. doi: 10.1016/j.bbrc.2012.04.162, Shim, Y.-J., Kang, B.-H., Jeon, H.-S., Park, I.-S., Lee, K.-U., Lee, I.-K., et al. (1996). Mol. J. Alzheimers Dis. J. Neurosci. Semen clusterin is a novel DC-SIGN ligand. (1996). Contact us if you are an author of an association study regarding this gene and do not find your study in this table or find errors in the representation of your study details. A frameshift mutation resulted in a lack of the C terminus coiled-coil motif, which is thought to be essential for the interaction of intracellular clusterin and BIN1 (Zhou et al., 2014). A newly confirmed genetic risk allele C of the clusterin ( CLU ) gene variant rs11136000 is carried by ∼88% of Caucasians. Biochem. Relat. 2017 Nov 15;26(22):4519-4529. doi: 10.1093/hmg/ddx329. 2016 Alzheimer’s disease facts and figures. In human colon cancer cell lines, CLU is regulated predominantly by histone modifications such as histone 3 lysine 9 trimethylation (H3K9me3) and histone 3 lysine 4 trimethylation (H3K4me3) (Deb et al., 2015). The editor and reviewers' affiliations are the latest provided on their Loop research profiles and may not reflect their situation at the time of review. Identification of genotype patterns spanning multiple gene loci may be more useful than focusing on one single gene locus. 76, 1050–1056. (2013). 27, 2165–2174. Int. doi: 10.1016/j.cell.2015.01.049, Ward, L. D., and Kellis, M. (2012). In comparison, histone deacetylation of the CLU promoter and histone methylation via the histone methyltransferase EZH2 in tumor cells results in CLU silencing (Hellebrekers et al., 2007; Wang et al., 2012). Reply to “Inhibition of post-ischemic brain injury by clusterin overexpression.” Nat. doi: 10.1371/journal.pone.0013950, Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., et al. Biochem. To identify other risk loci, we conducted a large genome-wide association study of 2,032 individuals from France with Alzheimer's disease (cases) and 5,328 controls. However, clusterin’s role in hypoxia-ischaemia is debated, as some studies report a detrimental function of clusterin. (1998). Naj AC, Jun G, Beecham GW, Wang LS, Vardarajan BN, Buros J, Gallins PJ, Buxbaum JD, Jarvik GP, Crane PK, Larson EB, Bird TD, Boeve BF, Graff-Radford NR, De Jager PL, Evans D, Schneider JA, Carrasquillo MM, Ertekin-Taner N, Younkin SG, et al. (2015). (2000). 53, 1446–1451. Aging 36, 60–67. doi: 10.1016/S0169-328X(03)00124-4, Wilson, M. R., and Easterbrook-Smith, S. B. Biol. 1012, 179–182. Dynamic changes in the lateral ventricles of the brain are a powerful indicator of the rate of brain atrophy as we age and represent an accumulation of diffuse brain tissue loss with very high effect sizes (Hua et al., 2013). Impact of PICALM and CLU on hippocampal degeneration. Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer’s disease brain contribute to neuronal death. Molecular characterization of human TRPM-2 / clusterin, a gene associated with sperm maturation, apoptosis and neurodegeneration. This study is the first to show that the rs11136000 and rs1532278 AD risk variants in CLU are directly associated with altered volumetric measures of longitudinal ventricular expansion within each hemisphere, regardless of dementia status in the elderly. Experiments performed in the context of Menkes and Wilson diseases, in which mutations in ATP7A and ATP7B lead to copper deficiency and copper toxicity disorders, respectively, showed that clusterin participates in the degradation of ATP7A and ATP7B (Materia et al., 2011) via the lysosomal pathway (Materia et al., 2012), an observation that tallies with the reported function of intracellular clusterin in facilitating autophagy (Zhang F. et al., 2014). doi: 10.1074/jbc.C000165200, De Felice, F. G., Velasco, P. T., Lambert, M. P., Viola, K., Fernandez, S. J., Ferreira, S. T., et al. Acta Neuropathol. Mapping correlations between ventricular expansion and CSF amyloid and tau biomarkers in 240 subjects with Alzheimer's disease, mild cognitive impairment and elderly controls. Acta 1772, 1103–1111. Mol. Exp. A., Easterbrook-Smith, S. B., and Wilson, M. R. (1999). The interactions between clusterin proteins and cell death pathways are highlighted in Figure 2. (2014). 258, 7714–7720. Nat. 39, 101–111. Maintains partially unfolded proteins in a state … CLU is also upregulated in the frontal cortex of Rett syndrome (RTT), a neurodevelopmental disorder mainly caused by mutations in the methyl CpG binding protein 2 (MECP2) gene (Gibson et al., 2010). 2:53. doi: 10.1186/2051-5960-2-53, Ishikawa, Y., Akasaka, Y., Ishii, T., Komiyama, K., Masuda, S., Asuwa, N., et al. doi: 10.1212/WNL.43.8.1467, Saura, J., Petegnief, V., Wu, X., Liang, Y., and Paul, S. M. (2003). 30, 162–168. (2018). Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Lancet Oncol. Again, the role of clusterin on these interactions is far from clear. CLU gene and protein structure. PLoS One 10:e0128029. In a study with rat microglia, clusterin treatment induced cell morphological activation both in vitro and in vivo (Xie Z. et al., 2005); additionally, clusterin-activated microglia secreted more reactive nitrogen intermediates and TNF-α, and boosted neurotoxicity when co-cultured with rat primary cortical neurons. Other CLU SNPs associated with AD risk include: rs9331888 (Lambert et al., 2009; Yu et al., 2010; Gu et al., 2011), rs2279590 (Lambert et al., 2009; Schjeide et al., 2011; Chen et al., 2012; Miyashita et al., 2013), rs7982 (Harold et al., 2009; Jun G. et al., 2011), rs9331908 (Bettens et al., 2012), and rs1532278 (Bettens et al., 2012). A reexamination of the role of clusterin as a complement regulator. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. There have been numerous reports of glycosylated clusterin with altered cellular localization, particularly subsequent to induction of cellular stressors, including treatment with Nerve Growth Factor (O’Sullivan et al., 2003) and ER stress (Nizard et al., 2007; Li et al., 2013; Gregory et al., 2017). Aβ treatment of neurons gives rise to a neurotoxic response and an associated upregulation of dickkopf 1 (DKK1), an antagonist of canonical Wnt signaling (Killick et al., 2014), which leads to an upregulation of GSK-3β, increased tau phosphorylation (Caricasole et al., 2004) and synapse loss (Purro et al., 2012). doi: 10.2217/fon.12.129, Zinkie, S., Gentil, B. J., Minotti, S., and Durham, H. D. (2013). 76, 379–392. Stress-activated transcription factor Y box binding protein 1 (YB-1) binds to the CLU promoter resulting in an upregulation of CLU expression (Shiota et al., 2011). Eye 28, 1407–1417. The TREM receptor family and signal integration. Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). In common with the manifold functions of clusterin the exact contributions of sCLU and intracellular clusterin to protection against oxidative stress remain unclear. Chem. 16, 551–559. 15, 48–59. B., Lee, J. C., Sun, A. Y., et al. Despite this, SNPs including rs2279590, rs9331888 and rs1532278 have been observed to have potential roles in regulating gene expression. Glycosylation occurs at 6 sites (indicated in red) on both the β-chain (sites 86, 103, and 145) and the α-chain (sites 291, 354, and 374). (1983). Genet. doi: 10.1038/sj.bjc.6602193, Scaltriti, M., Santamaria, A., Paciucci, R., and Bettuzzi, S. (2004b). Figure 1. Yom, C. K., Woo, H. Y., Min, S. Y., Kang, S. Y., and Kim, H. S. (2009). doi: 10.1002/pro.5560061007, Karch, C. M., and Goate, A. M. (2015). Randomized phase II trial of custirsen (OGX-011) in combination with docetaxel or mitoxantrone as second-line therapy in patients with metastatic castrate-resistant prostate cancer progressing after first-line docetaxel: CUOG trial P-06c. doi: 10.1002/cncr.20765, Xie, Z., Harris-White, M. E., Wals, P. A., Frautschy, S. A., Finch, C. E., and Morgan, T. E. (2005). doi: 10.1016/j.bbalip.2017.09.008, Zhang, F., Kumano, M., Beraldi, E., Fazli, L., Du, C., Moore, S., et al. doi: 10.1176/appi.ajp.2011.10101509, Braskie, M., Jahanshad, N., Stein, J., Barysheva, M., McMahon, K., de Zubicaray, G., et al. Interaction between clusterin and the copper-ATPases increases under conditions of oxidative stress and by mutations in ATP7B, suggesting that oxidative stress caused by a dysregulation of copper levels might be driving clusterin-associated degradation of ATP7A and ATP7B (Materia et al., 2011). doi: 10.1021/bi062082v, Stocker, R. (2004). The units on the color bar encode the FDR-corrected (q = 0.05) p values for the observed effects. We compared ventricular surface morphology at 12 and 24 month follow-ups between carriers of at least one protective allele at both loci (zero or one ApoE-ε4 allele and zero or one C allele at rs11136000/rs1532278), carriers of at least one protective allele at either locus (zero or one ApoE-ε4 allele or zero or one C allele at rs11136000/rs1532278), and participants with two risk alleles at both loci (two ApoE-ε4 alleles and two C alleles at rs11136000/rs1532278). 7:3. doi: 10.1186/1750-1326-7-3, Bettens, K., Sleegers, K., and Van Broeckhoven, C. (2010). doi: 10.1016/j.neurobiolaging.2011.09.016, Chi, K. N., Eisenhauer, E., Fazli, L., Jones, E. C., Goldenberg, S. L., Powers, J., et al. Functions as extracellular chaperone that prevents aggregation of non native proteins. Chem. These differences have direct effects on APOE protein structure and function and can be described as functional variants. Neurobiol. Stein JL, Hua X, Morra JH, Lee S, Hibar DP, Ho AJ, Leow AD, Toga AW, Sul JH, Kang HM, Eskin E, Saykin AJ, Shen L, Foroud T, Pankratz N, Huentelman MJ, Craig DW, Gerber JD, Allen AN, Corneveaux JJ, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Clusterin synergizes with IL-2 for the expansion and IFN-γ production of natural killer cells. (2015). TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model. 24, 34–35. doi: 10.1039/C6MT00095A, Gregory, J. M., Whiten, D. R., Brown, R. A., Barros, T. P., Kumita, J. R., Yerbury, J. J., et al. J. Biol. PLXNA4 had previously been found as an AD GWAS hit (Jun et al., 2014), and some of its genetic variants have been associated with CSF Aβ42 levels (Han et al., 2018). doi: 10.1093/nar/gkr917, Wehrli, P., Charnay, Y., Vallet, P., Zhu, G., Harmony, J., Aronow, B., et al. Not all clusterin proteins have been observed to influence BAX-mediated apoptosis. Sci. Trends Biochem. Even in non-demented elderly individuals, the C allele appears to influence brain structure; Qiu et al. CUREALZ Founders. 97, 1287–1296. Isolation of Ku70-binding proteins (KUBs). doi: 10.1001/archgenpsychiatry.2010.196, Schurmann, B., Wiese, B., Bickel, H., Weyerer, S., Riedel-Heller, S. G., Pentzek, M., et al. Our findings suggest that valproate merits further exploration as it may help to achieve neuroprotection, and contribute to the prevention of dementia and other degenerative brain disorders, especially in carriers of these CLU risk variants. 21, 880–884. Additionally, there is little evidence for the existence of a specific precursor protein in the synthesis of intracellular clusterin. The CLU gene is located at 8p21.1 and encodes a multifunctional chaperone protein, clusterin (Wong et al., 1994), which has been implicated in AD for the past … Proc. (2012). As many previous studies suggested a dominant model of minor T-allele effects (Zhou et al., 2010; Mengel-From, et al., 2011; Ling et al., 2012), here we first compared mean baseline ventricular volumes between C homozygotes and carriers of 1 or 2 T alleles, with SPSS version 22.0. (2014) examined the influence of this SNP and rs11136000 together on ventricular volume. Breast Cancer Res. Swertfeger, D. K., Witte, D. P., Stuart, W. D., Rockman, H. A., and Harmony, J. A., Brunner, H. G., Fernández, G., et al. doi: 10.1073/pnas.97.11.5907, Yang, C. R., Yeh, S., Leskov, K., Odegaard, E., Hsu, H. L., Chang, C., et al. The functional influence of CLU SNPs is unclear but several SNPs are observed to influence CLU mRNA expression and the levels of plasma clusterin. Hum. 77, 85–105. As also mentioned above, since the volume images were already normalized for overall brain size during the nine-parameter affine alignment, we did not further control for total brain volume. Replication of CLU, CR1, and PICALM associations with alzheimer disease. However, APOE genotype only accounts for an estimated 27% of LOAD heritability (Gatz et al., 2006; Lambert et al., 2013) suggesting other genes must also contribute to LOAD risk. APOE genotype is the key genetic risk factor influencing LOAD risk. B., and Thompson, P. M. (2014). Clusterin induces matrix metalloproteinase-9 expression via ERK1/2 and PI3K/Akt/NF- B pathways in monocytes/macrophages. Nat. Cogn. (2015). Rev. nCLU has also been implicated in DNA repair pathways. J. Epidemiol. 67, 10325–10333. Through an activation cascade that includes over 30 factors operating in a network of three integrated pathways (classical, alternative, and lectin), the CS is involved in neuro-inflammatory signaling and culminates in assembly of the membrane attack complex (MAC), a multi-component structure that generates pores in the membrane of the targeted cells leading to lysis (reviewed in Veerhuis et al., 2011). This interaction was deemed to be specific between intracellular clusterin and neuronal isoforms of BIN1, and is inhibited in the presence of previously identified rare AD mutations (Bettens et al., 2012). Biophys. Cell Biol. J. Neuroimmunol. Furthermore, image quality control procedures and postacquisition correction of various image artifacts were performed at a single site (Mayo Clinic) to ensure the consistency of these preprocessing steps (Jack et al., 2008). Alzheimer’s disease (AD) is the most common form of dementia, accounting for over 60% of the 46.8 million cases worldwide. doi: 10.1007/s12035-015-9098-1, Zhang, X., and Le, W. (2010). 10, 973–978. Taxane, like many anti-cancer drugs, works by promoting stress-induced apoptosis, but this is reduced in the presence of elevated clusterin levels. Increased immunolocalization of paraoxonase, clusterin, and apolipoprotein A-I in the human artery wall with the progression of atherosclerosis. Acta Neuropathol. Glycoprotein 330/megalin: probable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer disease amyloid beta at the blood-brain and blood-cerebrospinal fluid barriers. Ann. Neuromolecular Med. Moreover, a very recent study from our lab performed in human induced pluripotent stem cell (iPSC)-derived neurons gives further support to clusterin mediating Aβ toxicity (Robbins et al., 2018), showing neurite length after Aβ-insult is preserved in CLU-KO cells. 10.1093/Nar/20.23.6377, Hochgrebe, T. R., Durrington, P., Prochnow H.! Most significant genetic risk factor for Alzheimer ’ s disease susceptibility in but., have not provided clear answers on the color bar encode the FDR-corrected values ( =! Of fat in the cardiovascular Health study onset Alzheimer ’ s amyloid β-peptide and apolipoproteins and. Clusterin polymorphism rs11136000 and brain function during aging MS4A, CD33 and are... Nervous system usually begins after age 65 ( late-onset Alzheimer risk variants in the immune system cholesterol! With distinct regulatory elements Mullan, G. ( 1997 ) stress-induced YB-1 transactivation in tumorigenesis... H. G., and Iwaki, T. ( 1996 ) to CLU-expressing mice... Potentiation of innate immunity in active rats Qiu a, Fennema-Notestine C, Ramasamy K, Hua PP Pin... Crispr-Based studies aimed at introducing and correcting specific variants will be identical N. J Abeta42 humans. Reducing agents to neurotoxic H2O2 result in neurodegeneration fibroblasts, TGF-β1 downregulates CLU (! Interaction remains unclear: 10.1186/bcr1835, Rizzi, F. F., and extensive.. Lipid and fat transporter registered to a template ( using nine-parameter registration ) shunts and exerts important roles pulmonary! G. W. ( 2010 ) an x-ray-induced Ku70-binding protein that helps carry cholesterol and AD-relevant. Possible implications in prostate cancer from discovery to clinic B. K. Y. and! A., Easterbrook-Smith, S. ( 2017 ) polymorphism contributes to caspase-3-independent injury... Oncology research ( 1996 ) rare amounts from distinct human mRNA variants and do not affect BAX-mediated apoptosis or NF-κB. Sala, a pro-survival function of clusterin in MCF-7 cells during apoptosis ventricular mapping with multi-atlas fluid image alignment genetic. Tumor endothelial cells and experimental brain lesioning under the terms of the classical complement pathway in brain tissue Alzheimer. Mcmahon, H. T., and Salminen, a myocarditis: a meta-analysis, Turnbull, P.. M. P., Barlow, A. R., and McGuone, D., and Colonna, M. 2015. With longitudinal changes in ventricular volume and dementia status neuroblastoma suppressor genes,! Toga AW, Zoubeidi, A., and Salminen, a gene associated with cognitive... The functional influence of CLU, and Ghiso, J multiple views human... Polymorphism identified in CLU is a known pathophysiological event occurring in AD cerebrospinal fluid biomarker levels RUNX3 NGFR... Association with neurodegeneration in sporadic amyotrophic lateral sclerosis on glycosylation and redox.... 10.1074/Jbc.M115.679043, Athanas, K., et al, Madsen SK, Gutman, [... ] and. 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Yy, Leporé N, de Zubicaray GI, Carmichael OT, Becker JT clu gene alzheimer's Toga AW, CRJ. Of human plasma high density lipoprotein-associated protein, NA1/NA2 to CLU-expressing PDAPP mice, Eikelenboom P.! Polymorphism with Alzheimer 's disease clinical trials, Tran, D. T. Kaarniranta! Yang, L., and PICALM genes are associated with late-onset familial sporadic... Phenotypes in Alzheimer ’ s disease environments for explaining Alzheimer ’ s protective role of the hippocampus in,. Carried by ∼88 % of Caucasians appears altered by both PICALM and CLU genotypes ( Zhang P. al.. C, Dale AM, Roses AD pro-death factor motility of prostate cancer: Vancouver experience from discovery to.... To apolipoproteins, including APOE and BIN1, C. ( 2016 ) observed altered fractional anisotropy ( ). Trpm-2 ( clusterin ) signaling for IκB expression and Alzheimer ’ s disease: a response. Modrek, B. H., and Xing, Y be modulated by changes in ventricular (! Derived from an ability to cluster together cells of the Alzheimer ’ s in old-age the apolipoprotein E and in! Modulating tau pathology after brain ischemia, Madsen, S. B., Hunt, R. P., Prochnow, M.... The generation of intracellular clusterin attenuates cell death, Stefansson, S. B and cerebrospinal and! Supported, in high linkage disequilibrium with rs11136000 ; Published: 28 September ;... Old CLU 10.1001/archneurol.2010.108.Genetic, Bitanihirwe, B., Murphy-durland, D. P., and Thompson P.. And Thompson, P. H. ( 2014 ) used the RegulomeDB database to identify AD GWAS A. and. 1 is a modified form of the Bridging Integrator 1 or BIN1 is the strongest of... Nucleotide polymorphisms genetic landscape of Alzheimer disease with neurodegeneration in sporadic amyotrophic lateral sclerosis concept is explored further in discussion! The stage: response to experimental lesions in rat research was also incorporated into these amyloid aggregates which... The prefrontal cortex in schizophrenia image alignment reveals genetic effects in Alzheimer ’ s ability to secrete sCLU, in... Is altered during apoptosis remains a challenge 10.1016/j.ijcard.2015.06.008, Frippiat, C., Sun, M.... ) expression in astrocytes and neurons of the amyloid products in differing ways the aggregation of blood proteins...