Association of Clusterin Levels in Cerebrospinal Fluid with Synaptic Degeneration Across the Alzheimer’s Disease Continuum

PURPOSE: Although emerging evidence has suggested that clusterin is involved in the pathogenesis of Alzheimer’s disease (AD), the association of clusterin with synaptic degeneration in living human is unclear. In the present study, we aimed to examine the association of CSF clusterin levels with synaptic degeneration in individuals with different severities of cognitive impairment. PATIENTS AND METHODS: In the present study, we compared levels of clusterin in CSF among individuals with normal cognition (NC), mild cognitive impairment (MCI), and AD. Further, linear regression models were performed to examine the association of CSF clusterin with neurogranin (NG, reflecting synaptic degeneration) with adjustment of several potential confounders. RESULTS: We found that CSF clusterin levels were positively correlated with NG in the NC and MCI groups, but not the AD group. In all subjects, linear regression models suggested that clusterin levels were positively associated with NG levels independent of age, gender, apolipoprotein E4 (APOE4) genotype, clinical diagnosis, and CSF Aβ42 levels. CONCLUSION: Our data indicated that clusterin was associated with CSF NG levels among older individuals with different severities of cognitive impairment.