Differentiation of clinically diagnosed patients with aMCI and dementia from cognitively unimpaired older adults using plasma and serum p‐tau 181 and NfL

Background Blood‐based biomarkers give the possibility of having a less invasive, more acceptable to patients, and cost‐ and time‐efficient screening tool. Therefore, blood‐based biomarkers represent an ideal addition to cerebrospinal fluid (CSF) and neuroimaging biomarkers. Standard examination of neurocognitive disorders, such as lumbar punction or brain PET scan, cannot be performed within general practice. Given the high prevalence of these diseases, alternatives such as blood‐based biomarkers would represent a significant advance. The aim of this study was to investigate whether levels of p‐tau 181 and neurofilament light chain (NfL) in serum and plasma can differentiate cognitively unimpaired (CU) elderly individuals from individuals in the stage of aMCI and dementia. Method A total of 75 biomarker‐defined individuals from the Czech Brain Aging Study were recruited for the study, including the CU, individuals in the aMCI stage, and individuals in the stage of dementia syndrome with various etiology (AD, FTLD or LBD). Commercial ELISA kits were used for the assessment of standard biomarkers from CSF (Aß42, Aß40, pTau, tTau). Plasma and serum samples were analyzed using a Quanterix SR‐X analyzer with Simoa technology. Receiver operating characteristic analyses of the concentrations of p‐tau 181 and NfL in plasma and serum were performed using the R statistical software and GraphPad Prism. Result Plasma NfL, AUC 0.9861 (95% CI, 0.9439 to 1.000), and serum NfL with AUC 0.9583 (95% CI, 0.8774 to 1.000) differentiated aMCI and dementia from CU with high predictive accuracy. The results were significant for plasma p‐tau 181 too with AUC 0.7869 (95% CI, 0.6474 to 0.9265), along with serum p‐tau 181 with AUC 0.7623 (95% CI, 0.6292 to 0.8954). Conclusion Plasma and serum p‐tau 181 and NfL may be potentially useful and cost‐effective biomarkers for differentiating cognitively unimpaired elderly individuals from those at aMCI and dementia stages in general health care settings.