Cerebrospinal Fluid Biomarkers for the Diagnosis of Alzheimer Disease in South Korea

Abstract

Laboratory-specific reference values for cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers are necessary. Our objective was to apply well-known CSF biomarkers and redetermine their diagnostic cutoff values for AD in South Korea. CSF samples from matched control subjects (n=71), patients with AD dementia (ADD, n=76), and other neurological disorders with cognitive decline (OND, n=47) were obtained from 6 Korean dementia clinics according to a standardized protocol. CSF biomarker concentrations were measured using enzyme-linked immunosorbent assay. CSF biomarkers differed significantly between the ADD and control groups (P<0.001 for all), and between the ADD and OND groups (P<0.001 for all). The areas under the curve in differentiation of ADD from control subjects were 0.97 for Aβ42, 0.93 for total tau (tTau), 0.86 for pTau, and 0.99 for both tTau/Aβ42 and pTau/Aβ42 ratios. Our revised cutoff value for Aβ42 was higher than our previous one, whereas the values for the Tau proteins were similar. The tTau/Aβ42 ratio had the highest accuracy, 97%. Our findings highlight the usefulness of CSF AD biomarkers in South Korea, and the necessity of continually testing the reliability of cutoff values.

FIGURE 1

The CSF levels of Aβ42 (left), tTau (middle), and pTau181 (right) proteins depending on the diagnostic group. The CSF Aβ42 concentrations are lowest in ADD followed by OND and then control group, whereas CSF tTau and pTau181 proteins are most abundant in ADD than both OND and control subjects (P<0.001 in all). ANOVA with post hoc analysis using log-transformed CSF values of the individual AD biomarkers were used for group comparisons. The box plots show median and interquartile range with the whiskers representing 95% confidence interval (*P<0.05). ADD indicates Alzheimer disease dementia; ANOVA, analysis of variance; CON, controls; CSF, cerebrospinal fluid; OND, other neurological disorders with cognitive decline.