Wesley Jongbloed1, Karin D van Dijk2,3, Sandra D Mulder1,4, Wilma D J van de Berg2, Marinus A Blankenstein1, Wiesje van der Flier4, Robert Veerhuis1,5. 1. Department of Clinical Chemistry, Neurochemistry Laboratory, VU University Medical Center, Amsterdam, The Netherlands. 2. Department of Anatomy and Neurosciences, Section Functional Neuroanatomy, VU University Medical Center, Amsterdam, The Netherlands. 3. Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands. 4. VUmc Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. 5. Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
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.
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 ADpatients. Repeated MMSE was obtained for 44 MCI and 72 ADpatients 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 ADpatients (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: Liu Shi; Alison L Baird; Sarah Westwood; Abdul Hye; Richard Dobson; Madhav Thambisetty; Simon Lovestone Journal: J Alzheimers Dis Date: 2018 Impact factor: 4.472
Authors: Sofía Fernández-de-Retana; Mary Cano-Sarabia; Paula Marazuela; Jose Luis Sánchez-Quesada; Annabel Garcia-Leon; Alex Montañola; Joan Montaner; Daniel Maspoch; Mar Hernández-Guillamon Journal: Sci Rep Date: 2017-11-07 Impact factor: 4.379