CSF and blood Kallikrein-8: a promising early biomarker for Alzheimer’s disease

OBJECTIVE: There is still an urgent need for supportive minimally invasive and cost-effective biomarkers for early diagnosis of Alzheimer’s disease (AD). Previous work in our lab has identified Kallikrein-8 (KLK8) as a potential candidate since it shows an excessive increase in human brain in preclinical disease stages. The aim of this study was to evaluate the diagnostic performance of cerebrospinal fluid (CSF) and blood KLK8 for AD and mild cognitive impairment (MCI) due to AD. METHODS: In this multi-centre trans-sectional study, clinical and laboratory data as well as CSF and/or blood serum samples of 237 participants, including 98 patients with mild AD, 21 with MCI due to AD and 118 controls were collected. CSF and/or serum KLK8 levels were analysed by ELISA. The diagnostic accuracy of KLK8 in CSF and blood was determined using receiver operating characteristic (ROC) analyses and compared with that of CSF core biomarkers Aβ42, P-tau and T-tau. RESULTS: The diagnostic accuracy of CSF KLK8 was as good as that of core CSF biomarkers for AD (area under the curve (AUC)=0.89) and in case of MCI (AUC=0.97) even superior to CSF Aβ42. Blood KLK8 was a similarly strong discriminator for MCI (AUC=0.94) but slightly weaker for AD (AUC=0.83). CONCLUSIONS: This is the first study to demonstrate the potential clinical utility of blood and CSF KLK8 as a biomarker for incipient AD. Future prospective validation studies are warranted.