The clinical significance of plasma clusterin and Aβ in the longitudinal follow-up of patients with Alzheimer's disease

Background: Clusterin and beta-amyloid (Aβ) are involved in the pathogenesis of Alzheimer's disease (AD). The clinical significance of plasma clusterin and Aβ in AD progression remains controversial. Methods: We recruited 322 patients with AD and 88 controls between August 2012 and June 2013. All participants were evaluated at baseline with a clinical assessment, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) scales. Patients with AD were evaluated annually with the MMSE and Neuropsychiatric Inventory (NPI) scale during the 2-year follow-up period. The levels of plasma clusterin, Aβ1-40, and Aβ1-42 at baseline were analyzed to study the longitudinal changes in the patient scores on the MMSE and NPI during the follow-up period. Results: Patients in the highest tertile of plasma clusterin levels showed significantly lower MMSE scores than those in the lowest tertile (p = 0.04). After adjustment for multiple covariates using the generalized estimating equation analysis, there was a significant decrease in the MMSE scores over the 2-year follow-up period among AD patients in the highest tertile of plasma clusterin levels compared with those in the lowest tertile (-2.09, 95% confidence interval (CI) = -3.67 to -0.51, p = 0.01). In apolipoprotein E (ApoE)4-positive AD patients, baseline measurements of the ratio of plasma Aβ1-42/Aβ1-40 in the highest tertile predicted an increase in NPI agitation/aggression scores over the 2-year follow-up period (6.06, 95% CI = 1.20-10.62, p = 0.02). Conclusions: Plasma clusterin could serve as a biomarker for the severity of cognitive decline. Plasma Aβ in ApoE4-positive AD could predict long-term agitation/aggression symptoms.