Advertisement

Association between clusterin concentration and dementia: a systematic review and meta-analysis

  • Caiping Yang
  • Hai Wang
  • Chaojiu Li
  • Huiyan Niu
  • Shunkui Luo
  • Xingzhi Guo
Original Article
  • 59 Downloads

Abstract

Studies have showed that high clusterin (CLU) concentration was associated with increased risk of dementia. However, the results based on small samples remained controversial. The aim of our study was to determine the relationship between CLU concentration and the late-life cognitive outcomes including mild cognitive impairment (MCI), Alzheimer’s disease (AD), vascular dementia (VAD), Parkinson’s disease related dementia (PDD), Lewy body dementia (DLB) and frontotemporal dementia (FTD). A comprehensive search was conducted to screen the eligible studies in online database PubMed, Web of Science and Embase from 1950 to January 2017 according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. The CLU concentration data in brain tissue, cerebrospinal fluid (CSF), serum and plasma was collected to determine the strength of this association. The results were presented with standard difference of the mean (SDM) with 95% confidence intervals (CIs). A total of 28 studies were identified to calculate the association between CLU concentration and dementia. The results showed that the CLU concentration in the plasma (SDM = 0.73, 95% CI 0.26–1.19, P = 0.002) and brain tissue (SDM = 0.71, 95% CI 0.10–1.32, P = 0.022) was increased in dementia compared to normal control. Subgroup analysis showed that the plasma CLU concentration was significantly increased only in the AD group (SDM = 1.85, 95% CI 0.84–2.85, P < 0.001), but not in MCI or other dementias. No association was found between serum and CSF clusterin concentration and dementia. This meta-analysis indicates that high CLU concentration in the plasma and brain is associated with dementia, especially in AD.

Keywords

Clusterin Mild cognitive impairment Dementia Alzheimer’s disease Meta-analysis 

Notes

Compliance with ethical standards

Conflicts of interest

The authors declare no conflicts of interest.

Supplementary material

11011_2018_325_MOESM1_ESM.doc (30 kb)
ESM 1 (DOC 30 kb)

References

  1. Bertrand P, Poirier J, Oda T, Finch CE, Pasinetti GM (1995) Association of apolipoprotein E genotype with brain levels of apolipoprotein E and apolipoprotein J (clusterin) in Alzheimer disease. Brain Res Mol Brain Res 33:174–178CrossRefGoogle Scholar
  2. Bettens K, Vermeulen S, Van Cauwenberghe C, Heeman B, Asselbergh B, Robberecht C, Engelborghs S, Vandenbulcke M, Vandenberghe R, De Deyn PP, Cruts M, Van Broeckhoven C, Sleegers K (2015) Reduced secreted clusterin as a mechanism for Alzheimer-associated CLU mutations. Mol Neurodegener 10:30CrossRefGoogle Scholar
  3. Cai R, Han J, Sun J, Huang R, Tian S, Shen Y, Dong X, Xia W, Wang S (2016) Plasma Clusterin and the CLU gene rs11136000 variant are associated with mild cognitive impairment in type 2 diabetic patients. Front Aging Neurosci 8:179CrossRefGoogle Scholar
  4. Chen J, Wang M, Turko IV (2012) Mass spectrometry quantification of clusterin in the human brain. Mol Neurodegener 7:41CrossRefGoogle Scholar
  5. DeMattos RB, Cirrito JR, Parsadanian M, May PC, O'Dell MA, Taylor JW, Harmony JA, Aronow BJ, Bales KR, Paul SM, Holtzman DM (2004) ApoE and clusterin cooperatively suppress Abeta levels and deposition: evidence that ApoE regulates extracellular Abeta metabolism in vivo. Neuron 41:193–202CrossRefGoogle Scholar
  6. Deming Y, Xia J, Cai Y, Lord J, Holmans P, Bertelsen S, Holtzman D, Morris JC, Bales K, Pickering EH, Kauwe J, Goate A, Cruchaga C (2016) A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin. Neurobiol Aging 37:208.e1–208.e9CrossRefGoogle Scholar
  7. Desikan RS, Thompson WK, Holland D, Hess CP, Brewer JB, Zetterberg H, Blennow K, Andreassen OA, McEvoy LK, Hyman BT, Dale AM (2014) The role of clusterin in amyloid-beta-associated neurodegeneration. JAMA NEUROL 71:180–187CrossRefGoogle Scholar
  8. Du W, Tan J, Xu W, Chen J, Wang L (2016) Association between clusterin gene polymorphism rs11136000 and late-onset Alzheimer's disease susceptibility: a review and meta-analysis of case-control studies. EXP THER MED 12:2915–2927CrossRefGoogle Scholar
  9. Dukic L, Simundic AM, Martinic-Popovic I, Kackov S, Diamandis A, Begcevic I, Diamandis EP (2016) The role of human kallikrein 6, clusterin and adiponectin as potential blood biomarkers of dementia. Clin Biochem 49:213–218CrossRefGoogle Scholar
  10. Ferrari R, Moreno JH, Minhajuddin AT, O'Bryant SE, Reisch JS, Barber RC, Momeni P (2012) Implication of common and disease specific variants in CLU, CR1, and PICALM. Neurobiol Aging 33:1846–1847PubMedGoogle Scholar
  11. Golabek A, Marques MA, Lalowski M, Wisniewski T (1995) Amyloid beta binding proteins in vitro and in normal human cerebrospinal fluid. Neurosci Lett 191:79–82CrossRefGoogle Scholar
  12. Golebiewska EM, Poole AW (2015) Platelet secretion: from haemostasis to wound healing and beyond. Blood Rev 29:153–162CrossRefGoogle Scholar
  13. Gupta VB, Doecke JD, Hone E, Pedrini S, Laws SM, Thambisetty M, Bush AI, Rowe CC, Villemagne VL, Ames D, Masters CL, Macaulay SL, Rembach A, Rainey-Smith SR, Martins RN (2016) Plasma apolipoprotein J as a potential biomarker for Alzheimer's disease: Australian imaging. Biomarkers and Lifestyle Study of Aging Alzheimers Dement (Amst) 3:18–26Google Scholar
  14. Hakobyan S, Harding K, Aiyaz M, Hye A, Dobson R, Baird A, Liu B, Harris CL, Lovestone S, Morgan BP (2016) Complement biomarkers as predictors of disease progression in Alzheimer's disease. J Alzheimers Dis 54:707–716CrossRefGoogle Scholar
  15. Harr SD, Uint L, Hollister R, Hyman BT, Mendez AJ (1996) Brain expression of apolipoproteins E, J, and A-I in Alzheimer's disease. J Neurochem 66:2429–2435CrossRefGoogle Scholar
  16. Hughes TM, Lopez OL, Evans RW, Kamboh MI, Williamson JD, Klunk WE, Mathis CA, Price JC, Cohen AD, Snitz BE, Dekosky ST, Kuller LH (2014) Markers of cholesterol transport are associated with amyloid deposition in the brain. Neurobiol Aging 35:802–807CrossRefGoogle Scholar
  17. Ijsselstijn L, Dekker LJM, Koudstaal PJ, Hofman A, Sillevis Smitt PAE, Breteler MMB, Luider TM (2011) Serum clusterin levels are not increased in presymptomatic Alzheimers disease. J Proteome Res 10:2006–2010CrossRefGoogle Scholar
  18. Jongbloed W, Herrebout MA, Blankenstein MA, Veerhuis R (2014) Quantification of clusterin in paired cerebrospinal fluid and plasma samples. Ann Clin Biochem 51:557–567CrossRefGoogle Scholar
  19. Jongbloed W, van Dijk KD, Mulder SD, van de Berg WD, Blankenstein MA, van der Flier W, Veerhuis R (2015) Clusterin levels in plasma predict cognitive decline and progression to Alzheimer's disease. J Alzheimers Dis 46:1103–1110CrossRefGoogle Scholar
  20. Kim N, Choi WS (2011) Proapoptotic role of nuclear clusterin in brain. Anatomy & Cell Biology 44:169–175CrossRefGoogle Scholar
  21. Kim N, Yoo JC, Han JY, Hwang EM, Kim YS, Jeong EY, Sun CH, Yi GS, Roh GS, Kim HJ (2012) Human nuclear clusterin mediates apoptosis by interacting with Bcl-XL through C-terminal coiled coil domain. J Cell Physiol 227:1157–1167CrossRefGoogle Scholar
  22. Lidstrom AM, Bogdanovic N, Hesse C, Volkman I, Davidsson P, Blennow K (1998) Clusterin (apolipoprotein J) protein levels are increased in hippocampus and in frontal cortex in Alzheimer's disease. Exp Neurol 154:511–521CrossRefGoogle Scholar
  23. Lidstrom AM, Hesse C, Rosengren L, Fredman P, Davidsson P, Blennow K (2001) Normal levels of clusterin in cerebrospinal fluid in Alzheimer's disease, and no change after acute ischemic stroke. J Alzheimers Dis 3:435–442CrossRefGoogle Scholar
  24. Liu CC, Zhao N, Yamaguchi Y, Cirrito JR, Kanekiyo T, Holtzman DM, Bu G (2016) Neuronal heparan sulfates promote amyloid pathology by modulating brain amyloid-beta clearance and aggregation in Alzheimer's disease. Sci Transl Med 8:332r–344rGoogle Scholar
  25. Lu SJ, Li HL, Sun YM, Liu ZJ, Yang P, Wu ZY (2014) Clusterin variants are not associated with southern Chinese patients with Alzheimer's disease. Neurobiol Aging 35:2656–2659CrossRefGoogle Scholar
  26. Macaulay IC, Carr P, Gusnanto A, Ouwehand WH, Fitzgerald D, Watkins NA (2005) Platelet genomics and proteomics in human health and disease. J Clin Invest 115:3370–3377CrossRefGoogle Scholar
  27. Meng Y, Li H, Hua R, Wang H, Lu J, Yu X, Zhang C (2015) A correlativity study of plasma APL1beta28 and clusterin levels with MMSE/MoCA/CASI in aMCI patients. Sci Rep 5:15546CrossRefGoogle Scholar
  28. Mukaetova-Ladinska EB, Abdel-All Z, Dodds S, Andrade J, Alves Da Silva J, Kalaria RN, O'Brien JT (2012) Platelet immunoglobulin and amyloid precursor protein as potential peripheral biomarkers for Alzheimer's disease: findings from a pilot study. Age Ageing 41:408–412CrossRefGoogle Scholar
  29. Mukaetova-Ladinska EB, Abdel-All Z, Andrade J, Alves DSJ, O'Brien JT, Kalaria RN (2015) Plasma and platelet clusterin ratio is altered in Alzheimer's disease patients with distinct neuropsychiatric symptoms: findings from a pilot study. Int J Geriatr Psychiatry 30:368–375CrossRefGoogle Scholar
  30. Mullan GM, McEneny J, Fuchs M, McMaster C, Todd S, McGuinness B, Henry M, Passmore AP, Young IS, Johnston JA (2013) Plasma clusterin levels and the rs11136000 genotype in individuals with mild cognitive impairment and Alzheimer's disease. Curr Alzheimer Res 10:973–978CrossRefGoogle Scholar
  31. Nilselid AM, Davidsson P, Nagga K, Andreasen N, Fredman P, Blennow K (2006) Clusterin in cerebrospinal fluid: analysis of carbohydrates and quantification of native and glycosylated forms. Neurochem Int 48:718–728CrossRefGoogle Scholar
  32. Nuutinen T, Suuronen T, Kauppinen A, Salminen A (2009) Clusterin: a forgotten player in Alzheimer's disease. Brain Res Rev 61:89–104CrossRefGoogle Scholar
  33. Ossenkoppele R, van der Flier WM, Zwan MD, Adriaanse SF, Boellaard R, Windhorst AD, Barkhof F, Lammertsma AA, Scheltens P, van Berckel BN (2013) Differential effect of APOE genotype on amyloid load and glucose metabolism in AD dementia. Neurology 80:359–365CrossRefGoogle Scholar
  34. Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP (2013) The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 9:63–75CrossRefGoogle Scholar
  35. Puchades M, Hansson SF, Nilsson CL, Andreasen N, Blennow K, Davidsson P (2003) Proteomic studies of potential cerebrospinal fluid protein markers for Alzheimer's disease. Brain Res Mol Brain Res 118:140–146CrossRefGoogle Scholar
  36. Richens JL, Vere KA, Light RA, Soria D, Garibaldi J, Smith AD, Warden D, Wilcock G, Bajaj N, Morgan K, O'Shea P (2014) Practical detection of a definitive biomarker panel for Alzheimer's disease; comparisons between matched plasma and cerebrospinal fluid. International Journal of Molecular Epidemiology and Genetics 5:53–70PubMedPubMedCentralGoogle Scholar
  37. Savkovic V, Gantzer H, Reiser U, Selig L, Gaiser S, Sack U, Kloppel G, Mossner J, Keim V, Horn F, Bodeker H (2007) Clusterin is protective in pancreatitis through anti-apoptotic and anti-inflammatory properties. Biochem Biophys Res Commun 356:431–437CrossRefGoogle Scholar
  38. Schrijvers EM, Koudstaal PJ, Hofman A, Breteler MM (2011) Plasma clusterin and the risk of Alzheimer disease. JAMA 305:1322–1326CrossRefGoogle Scholar
  39. Schurmann B, Wiese B, Bickel H, Weyerer S, Riedel-Heller SG, Pentzek M, Bachmann C, Williams J, van den Bussche H, Maier W, Jessen F (2011) Association of the Alzheimer's disease clusterin risk allele with plasma clusterin concentration. J Alzheimers Dis 25:421–424CrossRefGoogle Scholar
  40. Shuai P, Liu Y, Lu W, Liu Q, Li T, Gong B (2015) Genetic associations of CLU rs9331888 polymorphism with Alzheimer's disease: a meta-analysis. Neurosci Lett 591:160–165CrossRefGoogle Scholar
  41. Silajdzic E, Minthon L, Bjorkqvist M, Hansson O (2012) No diagnostic value of plasma clusterin in Alzheimer's disease. PLoS One 7:e50237CrossRefGoogle Scholar
  42. Solomon A, Soininen H (2015) Dementia: risk prediction models in dementia prevention. NAT REV NEUROL 11:375–377CrossRefGoogle Scholar
  43. Song F, Poljak A, Crawford J, Kochan NA, Wen W, Cameron B, Lux O, Brodaty H, Mather K, Smythe GA, Sachdev PS (2012). Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals PLOS ONE 7Google Scholar
  44. Tan L, Wang HF, Tan MS, Tan CC, Zhu XC, Miao D, Yu WJ, Jiang T, Tan L, Yu JT (2016) Effect of CLU genetic variants on cerebrospinal fluid and neuroimaging markers in healthy, mild cognitive impairment and Alzheimer's disease cohorts. Sci Rep 6:26027CrossRefGoogle Scholar
  45. Thambisetty M, Simmons A, Velayudhan L, Hye A, Campbell J, Zhang Y, Wahlund LO, Westman E, Kinsey A, Guntert A, Proitsi P, Powell J, Causevic M, Killick R, Lunnon K, Lynham S, Broadstock M, Choudhry F, Howlett DR, Williams RJ, Sharp SI, Mitchelmore C, Tunnard C, Leung R, Foy C, O'Brien D, Breen G, Furney SJ, Ward M, Kloszewska I, Mecocci P, Soininen H, Tsolaki M, Vellas B, Hodges A, Murphy DG, Parkins S, Richardson JC, Resnick SM, Ferrucci L, Wong DF, Zhou Y, Muehlboeck S, Evans A, Francis PT, Spenger C, Lovestone S (2010) Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease. Arch Gen Psychiatry 67:739–748CrossRefGoogle Scholar
  46. Thambisetty M, An Y, Kinsey A, Koka D, Saleem M, Guntert A, Kraut M, Ferrucci L, Davatzikos C, Lovestone S, Resnick SM (2012) Plasma clusterin concentration is associated with longitudinal brain atrophy in mild cognitive impairment. NeuroImage 59:212–217CrossRefGoogle Scholar
  47. Trougakos IP (2013) The molecular chaperone apolipoprotein J/clusterin as a sensor of oxidative stress: implications in therapeutic approaches - a mini-review. Gerontology 59:514–523CrossRefGoogle Scholar
  48. Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, Ames D, Rowe CC, Masters CL (2013) Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol 12:357–367CrossRefGoogle Scholar
  49. Vishnu VY, Modi M, Sharma S, Mohanty M, Goyal MK, Lal V, Khandelwal N, Mittal BR, Prabhakar S (2016) Role of plasma Clusterin in Alzheimer's disease-a pilot study in a tertiary Hospital in Northern India. PLoS One 11:e166369CrossRefGoogle Scholar
  50. Weinstein G, Beiser AS, Preis SR, Courchesne P, Chouraki V, Levy D, Seshadri S (2016) Plasma clusterin levels and risk of dementia, Alzheimer's disease, and stroke. Alzheimers Dement (Amst) 3:103–109Google Scholar
  51. Xing YY, Yu JT, Cui WZ, Zhong XL, Wu ZC, Zhang Q, Tan L (2012) Blood clusterin levels, rs9331888 polymorphism, and the risk of Alzheimer's disease. J Alzheimers Dis 29:515–519CrossRefGoogle Scholar
  52. Yerbury JJ, Poon S, Meehan S, Thompson B, Kumita JR, Dobson CM, Wilson MR (2007) The extracellular chaperone clusterin influences amyloid formation and toxicity by interacting with prefibrillar structures. FASEB J 21:2312–2322CrossRefGoogle Scholar
  53. Yu J, Tan L (2012) The role of clusterin in Alzheimer’s disease: pathways, pathogenesis, and therapy. Mol Neurobiol 45:314–326CrossRefGoogle Scholar
  54. Zhang S, Zhang D, Jiang Y, Wu L, Shang H, Liu J, Feng R, Liao M, Zhang L, Liu Y, Liu G, Li K (2015) CLU rs2279590 polymorphism contributes to Alzheimer's disease susceptibility in Caucasian and Asian populations. J Neural Transm (Vienna) 122:433–439CrossRefGoogle Scholar
  55. Zhou Y, Hayashi I, Wong J, Tugusheva K, Renger JJ, Zerbinatti C (2014) Intracellular clusterin interacts with brain isoforms of the bridging integrator 1 and with the microtubule-associated protein tau in Alzheimer's disease. PLoS One 9:e103187CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Caiping Yang
    • 1
  • Hai Wang
    • 1
  • Chaojiu Li
    • 2
  • Huiyan Niu
    • 1
  • Shunkui Luo
    • 3
  • Xingzhi Guo
    • 3
  1. 1.Department of NeurologyHospital of ZhuozhouZhuozhouChina
  2. 2.The Middle School Attached to Northwestern Polytechnical UniversityXi’anChina
  3. 3.Department of Endocrinology and Metabolismthe Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhaiChina

Personalised recommendations