Performance of the QPLEX™ Alz plus assay, a novel multiplex kit for screening cerebral amyloid deposition

Abstract

Background Alzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by the hallmark finding of cerebral amyloid deposition. Many researchers have tried to predict the existence of cerebral amyloid deposition by using easily accessible blood plasma samples, but the effectiveness of such strategies remains controversial. Methods We developed a new multiplex kit, the QPLEX™ Alz plus assay kit, which uses proteomics-based blood biomarkers to prescreen for cerebral amyloid deposition. A total of 300 participants who underwent Pittsburgh compound B (PiB)-positron emission tomography (PET) which allows imaging of cerebral amyloid deposition were included in this study. We compared the levels of QPLEX™ biomarkers between patients who were classified as PiB-negative or PiB-positive, regardless of their cognitive function. Logistic regression analysis followed by receiver operating characteristic (ROC) curve analysis was performed. The kit accuracy was tested using a randomized sample selection method. Results The results obtained using our assay kit reached 89.1% area under curve (AUC) with 80.0% sensitivity and 83.0% specificity. Further validation of the QPLEX™ Alz plus assay kit using a randomized sample selection method showed an average accuracy of 81.5%. Conclusions Our QPLEX™ Alz plus assay kit provides preliminary evidence that it can be used as blood marker to predict cerebral amyloid deposition but independent validation is needed.

Application of QPLEXTM biomarkers in cognitively normal individuals across a broad age range and diverse regions with cerebral amyloid deposition

“…We previously reported that our QPLEX TM biomarkers (Aβ1–40, POSTN, LGALS3BP, and ACE) showed significant differences between age-matched (age >55 years old) PiB − and PiB + participants (Fig. 1a ) 21 . In this study, we utilized biomarkers to determine whether amyloid accumulated within the CN group (CN − , n = 185, PiB-PET negative; CN + , n = 36, PiB-PET positive; Table 1 ) (Fig.…”

“…Previously, we identified blood biomarkers that can differentiate those with from those without cerebral amyloid deposition and suggested the possible relevance of these biomarkers in AD diagnosis 11 . Based on these blood biomarkers, the QPLEX TM Alz plus assay kit was developed, and the efficiency of its diagnostic performance was assessed by clinically applying it to a large population cohort >55 years of age involving CN, MCI, and AD groups 21 . In the present study, we focused on QPLEX TM biomarkers in CN individuals across a broad age range, including CN individuals <55 years of age.…”

“…All participants were recruited as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) and underwent appropriate clinical and neuropsychological assessments in accordance with the KBASE assessment protocol. The recruitment of participants, clinical diagnostic criteria for AD, and further information are detailed in our previous reports involving the same KBASE cohort 11 , 21 , 22 .…”

“…All quantification methods were detailed in our previous study 21 . Briefly, the QPLEX TM kit utilized Quantamatrix’s multiplex diagnostics platform (QMAP; Quantamatrix Inc., Seoul, Republic of Korea) 29 .…”

“…We developed a prescreening platform for PiB-PET positivity using this QPLEX TM panel for individuals >55 years old, including CN individuals and patients with MCI and dementia 21 . Here, we investigated the application of the QPLEX TM Alz plus assay kit to CN individuals for the early diagnosis of AD and aimed to demonstrate the applicability of this kit in distinguishing between CN individuals with and without amyloid burden, especially in restricted age groups (the 3 rd tertile group, >65 years), for an efficient diagnosis.…”