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 Aß42, 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 Aß42. 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.

CSF amyloid-ß peptides in neuropathologically diagnosed dementia with Lewy bodies and Alzheimer's disease.

Appropriate treatment of dementia requires biomarkers that provide an exact and differential diagnosis. We recently presented differentially expressed amyloid-ß (Aß) peptide patterns in cerebrospinal fluid (CSF) as biomarker candidates for neurochemical diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). The objective of the present study was to investigate CSF Aß peptide patterns in both neuropathologically and clinically defined diagnostic groups of AD and DLB. Using the quantitative Aß-SDS-PAGE/immunoblot, we analyzed CSF samples of neuropathologically defined patients with AD (definite AD, dAD; n = 11) and DLB (definite, dDLB; n = 12). We compared absolute and relative quantities of CSF Aß-peptides with a larger cohort of clinically diagnosed patients with probable AD (pAD; n = 71), probable DLB (pDLB; n = 32), and non-demented controls (NDC; n = 71). Each neuropathologically and clinically defined diagnostic group showed a similar relative distribution of CSF Aß-peptides (Aß(1-X%)). Aß(1-42%) was lowered in dAD compared to NDC (p = 1.6 × 10⁻7, but did not differ between dAD and pAD. Aß(1-40ox%) was elevated in dDLB as compared to NDC (p = 1.8 × 10⁻5, but did not differ between dDLB and pDLB. Thus, we were able to confirm previous results on Aß peptide patterns in neuropathologically characterized patients with AD and DLB. Our results underline the usefulness of the CSF Aß(1-42%) and Aß(1-40ox%) as diagnostic biomarkers for AD and DLB, respectively.