Clusterin Levels in Plasma Predict Cognitive Decline and Progression to Alzheimer's Disease

被引:63
作者
Jongbloed, Wesley [1 ]
van Dijk, Karin D. [3 ,4 ]
Mulder, Sandra D. [1 ,2 ]
van de Berg, Wilma D. J.
Blankenstein, Marinus A. [1 ]
van der Flier, Wiesje [2 ]
Veerhuis, Robert [1 ,5 ]
机构
[1] Vrije Univ Amsterdam Med Ctr, Dept Clin Chem, Neurochem Lab, NL-1007 MB Amsterdam, Netherlands
[2] Vrije Univ Amsterdam Med Ctr, VUmc Alzheimer Ctr, NL-1007 MB Amsterdam, Netherlands
[3] Vrije Univ Amsterdam Med Ctr, Funct Neuroanat Sect, Dept Anat & Neurosci, NL-1007 MB Amsterdam, Netherlands
[4] Vrije Univ Amsterdam Med Ctr, Dept Neurol, NL-1007 MB Amsterdam, Netherlands
[5] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, NL-1007 MB Amsterdam, Netherlands
关键词
Alzheimer's disease; apolipoprotein J; biomarker; cerebrospinal fluid; clusterin; disease progression; mild cognitive impairment; plasma; GENOME-WIDE ASSOCIATION; CEREBROSPINAL-FLUID; IDENTIFIES VARIANTS; APOLIPOPROTEIN-J; COMPLEMENT; RISK; BETA; EXPRESSION; BIOMARKERS; INHIBITOR;
D O I
10.3233/JAD-150036
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Increased clusterin levels have been reported in brain, cerebrospinal fluid (CSF), and plasma of Alzheimer's disease (AD) patients. Because changes are also observed in mild cognitive impairment (MCI), a possible relationship between clusterin levels and early neurodegenerative changes in AD was suggested. Objectives: To determine whether clusterin concentrations could 1) serve as a diagnostic marker for AD, 2) predict disease progression in MCI, and 3) correlate with AD-biomarkers. Methods: Clusterin levels in CSF and plasma, as well as AD biomarker levels of A beta(42), Tau, and pTau in CSF and Mini-Mental State Examination scores (MMSE) were determined in 67 controls, 50 MCI, and 107 AD patients. Repeated MMSE was obtained for 44 MCI and 72 AD patients after, on average, 2.7 years. Results: Elevated clusterin concentrations in plasma, but not in CSF, were a risk factor for AD (HR 18.6; 95% CI 2.8-122), and related to cognitive decline in MCI (r = -0.38; p < 0.01). An inverse relation between plasma clusterin levels and cognitive decline was observed in AD patients (r = 0.23; p = 0.05). In CSF, but not in plasma, clusterin levels correlated with Tau and pTau in all groups. Conclusion: Elevated plasma clusterin levels in MCI confer an increased risk for progression to AD, and more rapid cognitive decline. We speculate that clusterin levels in CSF may reflect its involvement in the earliest neurodegenerative processes associated with AD pathology. Whereas neither clusterin levels in CSF nor in plasma had diagnostic value, plasma clusterin levels may serve as a prognostic marker for AD.
引用
收藏
页码:1103 / 1110
页数:8
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