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 Aβ
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.
