Is kallikrein-8 a blood biomarker for detecting amnestic mild cognitive impairment? Results of the population-based Heinz Nixdorf Recall study

Background Kallikrein-8 (KLK8) might be an early blood-biomarker of Alzheimer's disease (AD). We examined whether blood KLK8 is elevated in persons with amnestic mild cognitive impairment (aMCI) which is a precursor of AD, compared to cognitively unimpaired (CU) controls. Methods Forty cases and 80 controls, matched by sex and age (+/- 3years), were participants of the longitudinal population-based Heinz Nixdorf Recall study (baseline: 2000-2003). Standardized cognitive performance was assessed 5 (T1) and 10 years after baseline (T2). Cases were CU at T1 and had incidental aMCI at T2. Controls were CU at T1 and T2. Blood KLK8 was measured at T2. Using multiple logistic regression the association between KLK8 in cases vs. controls was investigated by estimating odds ratios (OR) and 95% confidence intervals (95%CI), adjusted for inter-assay variability and freezing duration. Using receiver operating characteristic (ROC) analysis, the diagnostic accuracy of KLK8 was determined by estimating the area under the curve (AUC) and 95%CI (adjusted for inter-assay variability, freezing duration, age, sex). Results Thirty-seven participants with aMCI vs. 72 CU (36.7%women, 71.0 +/- 8.0 (mean +/- SD) years) had valid KLK8 measurements. Mean KLK8 was higher in cases than in controls (911.6 +/- 619.8 pg/ml vs.783.1 +/- 633.0 pg/ml). Fully adjusted, a KLK8 increase of 500pg/ml was associated with a 2.68 (1.05-6.84) higher chance of having aMCI compared to being CU. With an AUC of 0.92 (0.86-0.97), blood KLK8 was a strong discriminator for aMCI and CU. Conclusion This is the first population-based study to demonstrate the potential clinical utility of blood KLK8 as a biomarker for incipient AD.

Automated summary

Blood Kallikrein-8 (KLK8) may be an early blood biomarker for Alzheimer's disease (AD). Elevated KLK8 levels were observed in individuals with amnestic mild cognitive impairment (aMCI), a precursor to AD, compared to cognitively unimpaired controls. The study concluded that blood KLK8 showed strong discriminatory potential for differentiating between aMCI and cognitively unimpaired individuals, suggesting its clinical utility as a biomarker for incipient AD.