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• W2896984128 abstract "Blood based biomarkers for Alzheimer's disease (AD) are urgently required. Extracellular Tau (eTau), a candidate blood biomarker, is highly heterogeneous and the majority of eTau is C-terminally truncated1. Thus, we devised a series of immunoassays to quantify different forms of eTau. We report that when used in plasma a particular N-terminal tau assay (NTT1) can distinguish patients from controls. CSF and plasma were from discovery and validation cohorts of patients with AD dementia (AD), mild cognitive impairment-AD (AD-MCI), and cognitively normal controls (NC). CSF Aß1-42 and total tau (tau) were measured by a single operator using Innotest ELISA. Patients had an AD CSF profile (Aß1-42≤630 pg/ml, Tau/Aß1-42≥0.882); AD patients had MMSE 15-24/30, and AD-MCI had MMSE 25-29/30. NC had Aß1-42>630 pg/ml, Tau/Aß1-42≤0.52 and MMSE 28-30/30. The NTT1 immunoassay was performed using the SimoaTM platform and employs the anti-tau mAbs, BT2 and Tau12. One-way ANOVA were used to compare mean levels of NTT1-measured analyte between groups. Receiver operating characteristics (ROC) curves quantified the diagnostic ability of the plasma assay. Demographic and CSF characteristics for the discovery (AD=25, AD-MCI=21, NC=19) and validation (AD=23, AD-MCI=22, NC=41) cohorts are in Table 1. The two cohorts were well-matched for MMSE and Aß1-42; the AD patients in the validation cohort were older (p<0.0001) and had lower CSF tau levels (p<0.05) than those in the discovery cohort. Results of the NTT1 assays are shown in Figure 1. In the discovery cohort, the NTT1-measured analytes in both CSF and plasma were significantly higher in AD and AD-MCI compared to NC (Figure 1). In the validation cohort, plasma NTT1-measured analytes were again significantly higher in each patient group compared to controls (Figure 1). ROC analysis showed that plasma NTT1 separates controls from AD-MCI (AUC 0.88) and AD (AUC=0.956) in the discovery cohort; in the validation cohort the AUCs were 0.8 and 0.751 respectively. NTT1-measured analyte in CSF (A) and plasma (B) in the discovery cohort and plasma (C) in the validation cohort. Bars show one standard deviation either side of the mean. *** denotes p<0.001 and ** denotes p<0.01 (one-way ANOVA). Plasma NTT1 achieves good separation of AD and AD-MCI from NC in two independent cohorts, and may be a useful screening blood biomarker for AD pathology. Kanmert et al. 2015 J Neurosci 35(30):10851–10865. Weston et al. 2015 Alzheimers Dement (Amst) 1(4):440-446." @default.
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• W2896984128 date "2018-07-01" @default.
• W2896984128 modified "2023-10-16" @default.
• W2896984128 title "P1‐301: CERTAIN PLASMA N‐TERMINAL TAU FRAGMENTS ARE ELEVATED IN AD AND AD‐MCI COMPARED TO CONTROLS" @default.
• W2896984128 doi "https://doi.org/10.1016/j.jalz.2018.06.308" @default.
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