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Clusterin Levels in Plasma Predict Cognitive Decline and Progression to Alzheimer's Disease.
J Alzheimers Dis 2015; 46(4):1103-10JA

Abstract

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 Aβ42, 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.

Authors+Show Affiliations

Department of Clinical Chemistry, Neurochemistry Laboratory, VU University Medical Center, Amsterdam, The Netherlands.Department of Anatomy and Neurosciences, Section Functional Neuroanatomy, VU University Medical Center, Amsterdam, The Netherlands. Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.Department of Clinical Chemistry, Neurochemistry Laboratory, VU University Medical Center, Amsterdam, The Netherlands. VUmc Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.Department of Anatomy and Neurosciences, Section Functional Neuroanatomy, VU University Medical Center, Amsterdam, The Netherlands.Department of Clinical Chemistry, Neurochemistry Laboratory, VU University Medical Center, Amsterdam, The Netherlands.VUmc Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.Department of Clinical Chemistry, Neurochemistry Laboratory, VU University Medical Center, Amsterdam, The Netherlands. Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26402636

Citation

Jongbloed, Wesley, et al. "Clusterin Levels in Plasma Predict Cognitive Decline and Progression to Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 46, no. 4, 2015, pp. 1103-10.
Jongbloed W, van Dijk KD, Mulder SD, et al. Clusterin Levels in Plasma Predict Cognitive Decline and Progression to Alzheimer's Disease. J Alzheimers Dis. 2015;46(4):1103-10.
Jongbloed, W., van Dijk, K. D., Mulder, S. D., van de Berg, W. D., Blankenstein, M. A., van der Flier, W., & Veerhuis, R. (2015). Clusterin Levels in Plasma Predict Cognitive Decline and Progression to Alzheimer's Disease. Journal of Alzheimer's Disease : JAD, 46(4), pp. 1103-10. doi:10.3233/JAD-150036.
Jongbloed W, et al. Clusterin Levels in Plasma Predict Cognitive Decline and Progression to Alzheimer's Disease. J Alzheimers Dis. 2015;46(4):1103-10. PubMed PMID: 26402636.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clusterin Levels in Plasma Predict Cognitive Decline and Progression to Alzheimer's Disease. AU - Jongbloed,Wesley, AU - van Dijk,Karin D, AU - Mulder,Sandra D, AU - van de Berg,Wilma D J, AU - Blankenstein,Marinus A, AU - van der Flier,Wiesje, AU - Veerhuis,Robert, PY - 2015/9/25/entrez PY - 2015/9/25/pubmed PY - 2016/7/1/medline KW - Alzheimer’s disease KW - apolipoprotein J KW - biomarker KW - cerebrospinal fluid KW - clusterin KW - disease progression KW - mild cognitive impairment KW - plasma SP - 1103 EP - 10 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 46 IS - 4 N2 - 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 Aβ42, 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/26402636/Clusterin_Levels_in_Plasma_Predict_Cognitive_Decline_and_Progression_to_Alzheimer's_Disease_ L2 - https://content.iospress.com/openurl?genre=article&amp;id=doi:10.3233/JAD-150036 DB - PRIME DP - Unbound Medicine ER -