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.

中文翻译：

---

脑脊液和血液Kallikrein-8：阿尔茨海默氏病的有希望的早期生物标志物。

目的仍然迫切需要支持性的微创且具有成本效益的生物标记物，以早期诊断阿尔茨海默氏病（AD）。我们实验室以前的工作已将Kallikrein-8（KLK8）鉴定为潜在的候选药物，因为它显示出在临床前疾病阶段人脑过度增加。这项研究的目的是评估脑脊液（CSF）和血液KLK8对AD和AD引起的轻度认知障碍（MCI）的诊断性能。方法在这项多中心的横断面研究中，收集了237名参与者的临床和实验室数据以及脑脊液和/或血清样本，其中包括98例轻度AD患者，21例由于AD引起的MCI和118例对照。通过ELISA分析CSF和/或血清KLK8水平。使用接收器操作特征（ROC）分析确定KLK8在CSF和血液中的诊断准确性，并与CSF核心生物标志物Aβ42，P-tau和T-tau进行比较。结果CSF KLK8的诊断准确性与核心CSF生物标志物对AD的诊断准确性（曲线下面积（AUC）= 0.89）相同，在MCI情况下（AUC = 0.97）甚至优于CSFAβ42。血液KLK8对MCI的鉴别力相似（AUC = 0.94），对AD的鉴别力稍弱（AUC = 0.83）。结论这是首次证明血液和脑脊液KLK8作为早期AD的生物标志物的潜在临床效用。未来的前瞻性验证研究是必要的。结果CSF KLK8的诊断准确性与核心CSF生物标志物对AD的诊断准确性（曲线下面积（AUC）= 0.89）相同，在MCI情况下（AUC = 0.97）甚至优于CSFAβ42。血液KLK8对MCI的鉴别力相似（AUC = 0.94），对AD的鉴别力稍弱（AUC = 0.83）。结论这是首次证明血液和脑脊液KLK8作为早期AD的生物标志物的潜在临床效用。未来的前瞻性验证研究是必要的。结果CSF KLK8的诊断准确性与核心CSF生物标志物对AD的诊断准确性（曲线下面积（AUC）= 0.89）相同，在MCI情况下（AUC = 0.97）甚至优于CSFAβ42。血液KLK8对MCI的鉴别力相似（AUC = 0.94），对AD的鉴别力稍弱（AUC = 0.83）。结论这是首次证明血液和脑脊液KLK8作为早期AD的生物标志物的潜在临床效用。未来的前瞻性验证研究是必要的。