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

Alzheimers Res Ther. 2017 Nov 23;9(1):91. doi: 10.1186/s13195-017-0319-x.


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.

Keywords: Alzheimer’s disease; Clusterin; Predictor; Progression.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / blood*
  • Apolipoproteins E / genetics
  • Clusterin / blood*
  • Cognition Disorders / etiology
  • Disease Progression
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Peptide Fragments / blood*
  • Psychiatric Status Rating Scales
  • Statistics, Nonparametric


  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Clusterin
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)