A correlativity study of plasma APL1β28 and clusterin levels with MMSE/MoCA/CASI in aMCI patients

Abstract

Amnestic mild cognitive impairment (aMCI) is a sub-clinical condition characterized by memory deficits that are not severe enough to affect daily functioning. Here we investigated two potential biomarkers found in the cerebrospinal fluid of AD patients, APLP1-derived Aβ-like peptides 28 (APL1β28) and clusterin plasma levels, in terms of their relationship to cognitive function, as reflected in the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and the Cognitive Assessment Screening Instrument (CASI) in aMCI patients. Forty-seven aMCI patients and thirty-five age- and gender-matched healthy adult controls were recruited for this study. Using the ELISA method, we found that the mean concentrations of both APL1β28 and clusterin were not significantly different between the control and aMCI groups. The APL1β28 levels were positively correlated with clusterin and that both were negatively correlated with the MMSE scores of the aMCI patients. Clusterin levels were negatively correlated with the MoCA and CASI scores of the aMCI patients. Using multivariate analysis, the correlation between clusterin and MMSE/MoCA/CASI was independent of other AD risk factors including age, education, sex, body mass index and ApoE genotype. The data presented here demonstrate that plasma clusterin levels reflect cognitive function in aMCI patients.

Figure 1. Statistical correlations between MMSE scores and plasma concentrations of APL1β28 and clusterin.

Scatter plots show correlations in all subjects and separately in the individual diagnostic groups. Solid lines indicate linear regression. (A) MMSE scores in the aMCI group (red circle) negatively correlate with APL1β28 concentrations in plasma. (B) MMSE scores in the aMCI group (red circle) negatively correlate with clusterin concentrations in plasma. (C) Plasma concentrations of APL1β28 and clusterin show strong correlations in both the aMCI (red circle) and NC (black triangle) groups. Note: Statistical comparisons were made using the student’s t-test.

Figure 2. Statistical correlations between CASI and MoCA scores and plasma concentrations of APL1β28 and clusterin.

(A) CASI and MoCA scores in the aMCI group (red circle) negatively correlate with clusterin concentrations in plasma. (B) Plasma concentrations of APL1β28 do not correlate with CASI and MoCA scores in the aMCI or NC groups.

Figure 3. Statistical correlations between ApoE genotype, BMI and plasma concentrations of APL1β28 and clusterin in the aMCI or NC groups.

(A) No significant changes are observed in the APL1β28 and clusterin levels of the aMCI and NC groups. All summary graphs show a mean ± SEM. (B) Plasma concentrations of APL1β28 and clusterin do not correlate with BMI in the aMCI or NC groups.