title: Clusterin Levels in Plasma Predict Cognitive Decline and Progression to Alzheimer's Disease.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Clinical Chemistry, Neurochemistry Laboratory, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Wesley
authors.initials: W
authors.lastname: Jongbloed
authors.affiliation: 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.
authors.forename: Karin D
authors.initials: KD
authors.lastname: van Dijk
authors.affiliation: 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.
authors.forename: Sandra D
authors.initials: SD
authors.lastname: Mulder
authors.affiliation: Department of Anatomy and Neurosciences, Section Functional Neuroanatomy, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Wilma D J
authors.initials: WD
authors.lastname: van de Berg
authors.affiliation: Department of Clinical Chemistry, Neurochemistry Laboratory, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Blankenstein
authors.affiliation: VUmc Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Wiesje
authors.initials: W
authors.lastname: van der Flier
authors.affiliation: 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.
authors.forename: Robert
authors.initials: R
authors.lastname: Veerhuis
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid; D000704:Analysis of Variance; D051152:Clusterin / Q000097:blood*; D003072:Cognition Disorders / Q000150:complications*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D051152:Clusterin; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer’s disease; apolipoprotein J; biomarker; cerebrospinal fluid; clusterin; disease progression; mild cognitive impairment; plasma