Generic placeholder image

Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Systematic Review Article

Plasma Clusterin as a Potential Biomarker for Alzheimer’s Disease-A Systematic Review and Meta-analysis

Author(s): XinRui Shi, BeiJia Xie, Yi Xing and Yi Tang*

Volume 16, Issue 11, 2019

Page: [1018 - 1027] Pages: 10

DOI: 10.2174/1567205016666191024141757

open access plus


Background: Plasma clusterin has been reported to be associated with the pathology, prevalence, severity, and rapid clinical progress of Alzheimer’s Disease (AD). However, whether plasma clusterin can be used as a biomarker of AD is inconsistent and even conflicting.

Objective: We conducted this study to evaluate the potential of plasma clusterin as the biomarker of AD.

Method: PubMed, Embase, and Cochrane databases were systematically searched for studies on the relationship between plasma clusterin levels and AD diagnosis, risk and disease severity. We also compared the difference in Cerebrospinal Fluid (CSF) clusterin levels between AD and control groups. We converted and pooled data using standardized mean difference, Pearson linear regression model and the Cox regression model.

Results: A total of 17 articles and 7228 individuals, including 1936 AD were included. The quality ranged from moderate to high. There was no difference in plasma clusterin between AD and control groups (SMD= 0.19 [-0.10, 0.48], p=0.20). Plasma clusterin levels were not correlated with the risk (RR=1.03 [0.97-1.09], p=0.31), the MMSE scores (R=0.33 [-0.06, 0.71], p= 0.09), and the integrated neuropsychological measurements (R=0.21 [-0.20, 0.63], p=0.31) of AD. Additionally, there was no difference in CSF clusterin between AD and control groups (SMD=1.94 [ -0.49, 4.37], p=0.12).

Conclusion: Our meta-analysis suggested no relationship between plasma clusterin levels and the diagnosis, risk, and disease severity of AD and no difference in the CSF clusterin between AD and the control groups. Overall, there is no evidence to support plasma clusterin as a biomarker of AD based on the pooled results.

Keywords: Clusterin, Alzheimer's disease, dementia, biomarker, systematic review, meta-analysis.

Frankish H, Horton R. Prevention and management of dementia: a priority for public health. Lancet (London, England) 390(10113): 2614-5.(2017);
Alzheimer’s A. 2018 Alzheimer’s disease facts and figures. Alzheimers & Dementia 14(3): 367-425.(2018);
Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell 148(6): 1204-22.(2012);
Cao J, Hou J, Ping J, Cai D. Advances in developing novel therapeutic strategies for Alzheimer’s disease. Mol Neurodegener 13(1): 64.(2018);
Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 13(6): 614-29.(2014);
Sunderland T, Linker G, Mirza N, Putnam KT, Friedman DL, Kimmel LH, et al. Decreased beta-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. JAMA 289(16): 2094-103.(2003);
Morris E, Chalkidou A, Hammers A, Peacock J, Summers J, Keevil S. Diagnostic accuracy of (18)F amyloid PET tracers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 43(2): 374-85.(2016);
Hill E, Goodwill AM, Gorelik A, Szoeke C. Diet and biomarkers of Alzheimer’s disease: a systematic review and meta-analysis. Neurobiol Aging 76: 45-52.(2019);
Wilson MR, Zoubeidi A. Clusterin as a therapeutic target. Expert Opin Ther Targets 21(2): 201-13.(2017);
Islam K, Damiati S, Sethi J, Suhail A, Pan G. Development of a label-free immunosensor for clusterin detection as an alzheimer's biomarker. Sensors (Basel, Switzerland) 18(1) pii: E308(2018);
Nuutinen T, Suuronen T, Kauppinen A, Salminen A. Clusterin: a forgotten player in Alzheimer’s disease. Brain Res Rev 61(2): 89-104.(2009);
Wu ZC, Yu JT, Li Y, Tan L. Clusterin in Alzheimer’s disease. Advances in clinical chemistry 56: 155-73.(2012);
Gouras GK, Olsson TT, Hansson O. Beta-amyloid peptides and amyloid plaques in Alzheimer’s disease. Neurotherapeutics 12(1): 3-11.(2015);
Yu JT, Tan L. The role of clusterin in Alzheimer’s disease: pathways, pathogenesis, and therapy. Mol Neurobiol 45(2): 314-26.(2012);
Nelson AR, Sagare AP, Zlokovic BV. Role of clusterin in the brain vascular clearance of amyloid-beta. Proc Natl Acad Sci USA 114(33): 8681-2.(2017);
Li X, Ma Y, Wei X, Li Y, Wu H, Zhuang J, et al. Clusterin in Alzheimer’s disease: a player in the biological behavior of amyloid-beta. Neurosci Bull 30(1): 162-8.(2014);
Lidstrom AM, Bogdanovic N, Hesse C, Volkman I, Davidsson P, Blennow K. Clusterin (apolipoprotein J) protein levels are increased in hippocampus and in frontal cortex in Alzheimer’s disease. Exp Neurol 154(2): 511-21.(1998);
May PC, Lampert-Etchells M, Johnson SA, Poirier J, Masters JN, Finch CE. Dynamics of gene expression for a hippocampal glycoprotein elevated in Alzheimer’s disease and in response to experimental lesions in rat. Neuron 5(6): 831-9.(1990);
Zhu R, Liu X, He Z. Association between CLU gene rs11136000 polymorphism and Alzheimer’s disease. Neurol Sci 39(4): 679-89.(2018);
Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Transl Psychiatry 41(10): 1094-9.(2009);
Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet 41(10): 1088-93.(2009);
Schrijvers EMC, Koudstaal PJ, Hofman A, Breteler MMB. Plasma clusterin and the risk of Alzheimer disease. JAMA 305(13): 1322-6.(2011);
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 151(4): 264-9.(2009);
Lo CK, Mertz D, Loeb M. Newcastle-Ottawa Scale: comparing reviewers’ to authors’ assessments. BMC 14: 45.(2014);
Dukic L, Simundic AM, Martinic-Popovic I, Kackov S, Diamandis A, Begcevic I, et al. The role of human kallikrein 6, clusterin and adiponectin as potential blood biomarkers of dementia. Clin Biochem 49(3): 213-8.(2016);
Deming Y, Xia J, Cai Y, Lord J, Holmans P, Bertelsen S, et al. A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin. Neurobiol Aging 37: 208. .e1-.e9(2016);
Hsu JL, Lee WJ, Liao YC, Wang SJ, Fuh JL. The clinical significance of plasma clusterin and Abeta in the longitudinal follow-up of patients with Alzheimer’s disease. Alzheimers Res Ther 9(1): 91.(2017);
Ijsselstijn L, Dekker LJM, Koudstaal PJ, Hofman A, Sillevis SPAE, Breteler MMB, et al. Serum clusterin levels are not increased in presymptomatic Alzheimers disease. J Proteome Res 10(4): 2006-10.(2011);
Mukaetova-Ladinska EB, Abdel-All Z, Andrade J, Alves da Silva J, O’Brien JT, Kalaria RN. 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(4): 368-75.(2015);
Mullan GM, McEneny J, Fuchs M, McMaster C, Todd S, McGuinness B, et al. Plasma clusterin levels and the rs11136000 genotype in individuals with mild cognitive impairment and Alzheimer’s disease. Curr Alzheimer Res 10(9): 973-8.(2013);
Richens JL, Vere KA, Light RA, Soria D, Garibaldi J, Smith AD, et al. Practical detection of a definitive biomarker panel for Alzheimer’s disease; comparisons between matched plasma and cerebrospinal fluid. Int J Mol Epidemiol Genet 5(2): 53-70.(2014);
Schürmann B, Wiese B, Bickel H, Weyerer S, Riedel-Heller SG, Pentzek M, et al. Association of the Alzheimer’s disease clusterin risk allele with plasma clusterin concentration. J Alzheimers Dis 25(3): 421-4.(2011);
Silajdžić E, Minthon L, Björkqvist M, Hansson O. No Diagnostic value of plasma clusterin in Alzheimer’s disease. PLoS One 7(11)(2012);
Thambisetty M, Simmons A, Velayudhan L, Hye A, Campbell J, Zhang Y, et al. Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease. Arch Gen Psychiatry 67(7): 739-48.(2010);
Vishnu VY, Modi M, Sharma S, Mohanty M, Goyal MK, Lal V, et al. Role of plasma clusterin in Alzheimer’s disease-a pilot study in a tertiary hospital in Northern India. PLoS One 11(11) e0166369(2016);
Xing YY, Yu JT, Cui WZ, Zhong XL, Wu ZC, Zhang Q, et al. Blood clusterin levels, rs9331888 polymorphism, and the risk of Alzheimer’s disease. J Alzheimers Dis 29(3): 515-9.(2012);
Lidström AM, Hesse C, Rosengren L, Fredman P, Davidsson P, Blennow K. Normal levels of clusterin in cerebrospinal fluid in Alzheimer’s disease, and no change after acute ischemic stroke. J Alzheimers Dis 3(5): 435-42.(2001);
Weinstein G, Beiser AS, Preis SR, Courchesne P, Chouraki V, Levy D, et al. Plasma clusterin levels and risk of dementia, Alzheimer’s disease, and stroke. Alzheimer’s and dementia: diagnosis. Assess Dis Monit 3: 103-9.(2016);
Jongbloed W, Van Dijk KD, Mulder SD, Van De Berg WDJ, Blankenstein MA, Van Der Flier W, et al. Clusterin levels in Plasma Predict Cognitive Decline and Progression to Alzheimer’s Disease. J Alzheimers Dis 46(4): 1103-10.(2015);
Haight T, Bryan RN, Meirelles O, Tracy R, Fornage M, Richard M, et al. Associations of plasma clusterin and Alzheimer’s disease-related MRI markers in adults at mid-life: The CARDIA Brain MRI sub-study. PLoS One 13(1) e0190478(2018);
Thambisetty M, An Y, Kinsey A, Koka D, Saleem M, Guntert A, et al. Plasma clusterin concentration is associated with longitudinal brain atrophy in mild cognitive impairment. Neuroimage 59(1): 212-7.(2012);
Yang C, Wang H, Li C, Niu H, Luo S, Guo X. Association between clusterin concentration and dementia: a systematic review and meta-analysis. Metab Brain Dis 34(1): 129-40.(2019);
Dubois B, Padovani A, Scheltens P, Rossi A, Dell’Agnello G. Timely Diagnosis for Alzheimer’s Disease: A Literature Review on Benefits and Challenges. J Alzheimers Dis 49(3): 617-31.(2016);
Pinto TCC, Machado L, Bulgacov TM, Rodrigues-Junior AL, Costa MLG, Ximenes RCC, et al. Is the montreal cognitive assessment (moca) screening superior to the mini-mental state examination (mmse) in the detection of mild cognitive impairment (mci) and Alzheimer’s disease (AD) in the elderly? Int Psychogeriatr 31(4): 491-504.(2019);
Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 6(3): 131-44.(2010);
Wang P, Chen K, Gu Y, Guo Q, Hong Z, Zhao Q. beta-Amyloid Upregulates Intracellular Clusterin but not Secretory Clusterin in Primary Cultured Neurons and APP Mice. Curr Alzheimer Res 14(11): 1207-14.(2017);
Esteban JA. Living with the enemy: a physiological role for the beta-amyloid peptide. Trends Neurosci 27(1): 1-3.(2004);
Leo G, Genedani S, Filaferro M, Carone C, Andreoli N, Astancolle S, et al. Hyper-homocysteinemia alters amyloid peptide-clusterin interactions and neuroglial network morphology and function in the caudate after intrastriatal injection of amyloid peptides. Curr Alzheimer Res 4(3): 305-13.(2007);

© 2022 Bentham Science Publishers | Privacy Policy