Ultrasensitive assays for detection of plasma tau and phosphorylated tau 181 in Alzheimer’s disease: a systematic review and meta-analysis

Abstract

A lack of convenient and reliable biomarkers for diagnosis and prognosis is a common challenge for neurodegenerative diseases such as Alzheimer’s disease (AD). Recent advancement in ultrasensitive protein assays has allowed the quantification of tau and phosphorylated tau proteins in peripheral plasma. Here we identified 66 eligible studies reporting quantification of plasma tau and phosphorylated tau 181 (ptau181) using four ultrasensitive methods. Meta-analysis of these studies confirmed that the AD patients had significantly higher plasma tau and ptau181 levels compared with controls, and that the plasma tau and ptau181 could predict AD with high-accuracy area under curve of the Receiver Operating Characteristic. Therefore, plasma tau and plasma ptau181 can be considered as biomarkers for AD diagnosis.

Performance of Plasma Amyloid β, Total Tau, and Neurofilament Light Chain in the Identification of Probable Alzheimer's Disease in South China

“…In the present study, plasma t-tau levels were significantly higher in patients with probable AD than in healthy controls, similar to the findings of most published results (Mattsson et al, 2016 ; Lue et al, 2017 ), whereas several studies also found that plasma t-tau levels showed the opposite result or no significant difference between them (Sparks et al, 2012 ; Verberk et al, 2018 ; Qu et al, 2021 ). In a large meta-analysis, it was confirmed that patients with AD had higher plasma t-tau levels than controls, which may reflect neuronal damage as a nonspecific marker (Jack et al, 2018 ; Ding et al, 2021 ). Mattson et al found that the higher plasma t-tau level was associated with AD dementia and showed significant correlations with poor cognition, greater atrophy, and hypometabolism during follow-up in the AD Neuroimaging Initiative study (Mattsson et al, 2016 ).…”

Neuroprotective Effect of Trans-Resveratrol in Mild to Moderate Alzheimer Disease: A Randomized, Double-Blind Trial

“…In addition, increased CSF t-tau has been found in a variety of other neurological disorders, including frontotemporal dementia [ 4 , 5 , 34 ]. Further, CSF p-tau181 is a highly specific biomarker of AD pathology [ 4 , 5 , 34 ].…”

“…In addition, increased CSF t-tau has been found in a variety of other neurological disorders, including frontotemporal dementia [ 4 , 5 , 34 ]. Further, CSF p-tau181 is a highly specific biomarker of AD pathology [ 4 , 5 , 34 ]. Our results show that there was no difference in the level of CSF tau and p-tau181 (ESM Table 2) at baseline and treatment at week 52.…”

“…These inflammatory cytokines further act on peripheral glial cells to amplify the inflammatory response, forming a positive feedback loop, leading to the increased production of oxygen-free radicals that in turn accelerates deterioration of AD and ultimately leads to neuronal loss and a decline in cognitive function [ 2 , 3 ]. A characteristic sign of AD is the presence of tau proteins that are irregularly folded and aggregated into abnormal bundles of filaments [ 4 , 5 ]. Abnormal tau phosphorylation has also been found to be more strongly associated with AD than with total tau (t-tau) [ 4 , 5 ].…”

“…A characteristic sign of AD is the presence of tau proteins that are irregularly folded and aggregated into abnormal bundles of filaments [ 4 , 5 ]. Abnormal tau phosphorylation has also been found to be more strongly associated with AD than with total tau (t-tau) [ 4 , 5 ]. Consequently, AD is a disease with multiple etiologies and a complex pathogenesis.…”