Association between clusterin concentration and dementia: a systematic review and meta-analysis
- 196 Downloads
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.
KeywordsClusterin Mild cognitive impairment Dementia Alzheimer’s disease Meta-analysis
Compliance with ethical standards
Conflicts of interest
The authors declare no conflicts of interest.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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