Plasma biomarkers distinguish clinical diagnostic groups in memory clinic patients

Abstract

AbstractBackgroundPlasma biomarkers as a new approach in Alzheimer’s screening and diagnostics are time‐ and cost‐saving. Blood sampling is easier, less risky, and less invasive than other well‐established diagnostic tools, such as cerebrospinal fluid biomarkers (CSF), and is well tolerated by patients. The goal of this study was to test whether and to what extent plasma biomarkers are suitable for the differentiation between the clinical diagnostic groups dementia of Alzheimer’s type (DAT), mild cognitive impairment (MCI) and subjective cognitive decline (SCD) in a routine care memory clinic.MethodWe examined plasma samples of 144 memory clinic patients. Plasma biomarkers were measured through ultrasensitive Single molecule array (Simoa) immunoassay technology. The concentrations of amyloid‐beta42 (Aß42), amyloid‐beta40 (Aß40), phospho‐Tau181 (pTau181), total‐Tau (tTau) and neurofilament‐light (NF‐L) were determined. Statistical analysis, including receiver operating characteristics (ROC) analyses, were performed. Possible cut‐off values are discussed.ResultThrough Aß40 a weak differentiation between SCD and DAT (AUC=0.64) and through Aß42/Aß40 a weak differentiation between SCD and MCI (AUC=0.64), SCD and MCI+DAT (AUC=0.66) and SCD and DAT (AUC=0.67) was possible. PTau181 was able to distinguish between diagnostic groups and showed a weak differentiation between MCI and DAT (AUC=0.69), a strong differentiation between SCD and MCI+DAT (AUC=0.78) and SCD and MCI (AUC=0.72) and an excellent differentiation between SCD and DAT (AUC=0.85). NF‐L weakly distinguished between SCD and MCI+DAT (AUC=0.70) and MCI and DAT (AUC=0.72), but strongly distinguished between SCD and DAT (AUC=0.81). At a cut‐off point of 10.2pg/ml pTau181 showed a sensitivity of 89% and a specificity of 73% to distinguish between SCD and DAT.ConclusionPlasma Aß40, Aß42/Aß40, pTau181 and NF‐L analyzed with the Simoa technology proved to be promising future diagnostic and screening tools in a routine memory clinic setting outside of specific research studies. While amyloid markers showed only moderate discrimination between the groups, pTau181 and NF‐L clearly distinguished between SCD and the more progressed stages of MCI and DAT. These findings agree with the current model of amyloid build‐up already before significant clinical symptoms, and pTau and neurodegeneration correlating with symptomatic progression. In our data, pTau181 provided the best discrimination between the diagnostic groups.