Plasma tau complements CSF tau and P‐tau in the diagnosis of Alzheimer's disease

Abstract

Introduction Plasma tau may be an accessible biomarker for Alzheimer's disease (AD), but the correlation between plasma and cerebrospinal fluid (CSF) tau and the value of combining plasma tau with CSF tau and phospho-tau (P-tau) are still unclear. Methods Plasma-tau, CSF-tau, and P-tau were measured in 97 subjects, including elderly cognitively normal controls (n = 68) and patients with AD (n = 29) recruited at the NYU Center for Brain Health, with comprehensive neuropsychological and magnetic resonance imaging evaluations. Results Plasma tau was higher in patients with AD than cognitively normal controls ( P < .001, area under the receiver operating characteristic curve = 0.79) similarly to CSF tau and CSF P-tau and was negatively correlated with cognition in AD. Plasma and CSF tau measures were poorly correlated. Adding plasma tau to CSF tau or CSF P-tau significantly increased the areas under the receiver operating characteristic curve from 0.80 and 0.82 to 0.87 and 0.88, respectively. Discussion Plasma tau is higher in AD independently from CSF-tau. Importantly, adding plasma tau to CSF tau or P-tau improves diagnostic accuracy, suggesting that plasma tau may represent a useful biomarker for AD, especially when added to CSF tau measures.

Correlation between cognition and plasma noradrenaline level in Alzheimer’s disease: a potential new blood marker of disease evolution

“…Studies in this area have shown conflicting results with (i) no difference between AD and control patients 47,49,50 51,55 . Moreover, other studies have shown different linear correlations in the context of AD (i) between imaging data of amyloid plaque deposition in the brain and CSF 59 or plasma 46,48 biomarker concentrations and (ii) between CSF and plasma biomarker concentrations 45,47,50,57,58 . The mechanisms behind brain AD biomarker clearance pathways (blood-brain, CSF-brain and blood-CSF barriers) are not yet understood, and it is not clear if those barriers are altered during the disease.…”

“…The need to find alternative body fluids for biomarker identification in AD has recently led investigators to analyze currently known CSF biomarkers for AD in plasma [45][46][47][48][49][50][51][52][53][54][55][56][57] . Studies in this area have shown conflicting results with (i) no difference between AD and control patients 47,49,50 51,55 .…”

A soluble truncated tau species related to cognitive dysfunction is elevated in the brain of cognitively impaired human individuals

“…Soluble T-tau proteins were quantitatively measured using the Simoa Tau 2.0 reagent kit (Quanterix), which has been widely used in multiple published studies (see, for example [58][59][60] ). The LLOD and LLOQ are reported as 0.019 and 0.061 pg/mL, respectively.…”

Longitudinal evaluation of the natural history of amyloid-β in plasma and brain

“…Plasma Aβ has reported area under the receiver operating curve values of 90% for discriminating between brain Aβ positives and negatives ( Fandos et al , 2017 ; Ovod et al , 2017 ; Nakamura et al , 2018 ). In regard to the Aβ (A), tau (T) and neurodegeneration ([N]) framework ( Jack et al , 2018 ), recent reports show that plasma pTau can discriminate between controls and Alzheimer’s disease, achieving area under the receiver operating curve values of 80% ( Kovacs et al , 2017 ; Fossati et al , 2019 ). Along the same line, neurofilament light has emerged as an accurate plasma measure for Alzheimer’s disease progression and has been shown to discriminate between controls and Alzheimer’s disease, suggesting that it could be used as a robust marker of neurodegeneration ( Kovacs et al , 2017 ; Lewczuk et al , 2018 ; Mattsson et al , 2019 ).…”