Plasma tau proteins for the diagnosis of mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis

Chen, Leian; Niu, Xiaoqian; Wang, Yuye; Liu, Shuang; Zhou, Xiaofeng; Yang, Ziyuan; Peng, Dantao

doi:10.3389/fnagi.2022.942629

Cited by 11 publications

(12 citation statements)

References 39 publications

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“…Several p-tau biomarkers (p-tau217, p-tau231, and p-tau235) are well-established markers to diagnose AD dementia from non-AD controls. A recent meta-analysis suggested that p-tau217 had better discriminative accuracy for MCI than p-tau181 and p-tau231 ( Chen et al, 2022 ). We recently showed that a new neuropathological biomarker p-tau198 had capability to diagnose MCI cohorts from cognitively normal subjects in brain tissues ( Wu et al, 2022a ).…”

Section: Discussionmentioning

confidence: 99%

Differential diagnosis of mild cognitive impairment of Alzheimer’s disease by Simoa p-tau181 measurements with matching plasma and CSF

Wu,

Arvai,

Wang

et al. 2024

Front. Mol. Neurosci.

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Alzheimer’s disease (AD) is characterized by a long preclinical phase. Although late-stage AD/dementia may be robustly differentiated from cognitively normal individuals by means of a clinical evaluation, PET imaging, and established biofluid biomarkers, disease differentiation between cognitively normal and various subtypes of mild cognitive impairment (MCI) remains a challenging task. Differential biomarkers for early-stage AD diagnosis with accessible biofluid samples are urgently needed. Misfolded phosphorylated tau aggregates (p-tau) are present in multiple neurodegenerative diseases known as “tauopathies”, with the most common being AD. P-tau181 is a well-established p-tau biomarker to differentiate AD dementia from non-AD pathology. However, it is unclear if p-tau181 is capable of diagnosing MCI, an early AD stage, from cognitively normal subjects, or if it can discriminate MCI subtypes amnestic MCI (aMCI) from non-amnestic MCI (naMCI). Here we evaluated the capability of p-tau181 in diagnosing MCI from cognitively normal subjects and discriminating aMCI from naMCI subtypes. We collected matching plasma and CSF samples of a clinically diagnosed cohort of 35 cognitively normal, 34 aMCI, 17 naMCI, and 31 AD dementia cases (total 117 participants) with supplemental CSF Aβ42 and total tau AD biomarker levels and performed Simoa p-tau181 assays. The diagnostic capabilities of Simoa p-tau181 assays to differentiate these cohorts were evaluated. We found (i) p-tau181 can robustly differentiate MCI or aMCI from cognitively normal cohorts with matching plasma and CSF samples, but such differentiation is weaker in diagnosing naMCI from cognitively normal groups, (ii) p-tau181 is not capable of differentiating aMCI from naMCI cohorts, and (iii) either factor of Aβ or total tau burden markedly improved differentiation power to diagnose aMCI from cognitively normal group. Plasma and CSF p-tau181 levels may serve as a promising biomarker for diagnosing aMCI from normal controls in the preclinical phase. But more robust new biomarkers are needed to differentiate naMCI from cognitively normal cases or to discriminate between MCI subtypes, aMCI from naMCI.

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Section: Discussionmentioning

confidence: 99%

Differential diagnosis of mild cognitive impairment of Alzheimer’s disease by Simoa p-tau181 measurements with matching plasma and CSF

Wu,

Arvai,

Wang

et al. 2024

Front. Mol. Neurosci.

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“…First, it was only recently that Ashton et al pioneered the measurement of P‐tau231 concentrations in plasma (Ashton, Pascoal, et al, 2021). Second, a recent meta‐analysis of eligible literature published before 26 June 2021 provided an integrative account of plasma tau proteins for the diagnosis of MCI and AD (Chen et al, 2022), including only one article on plasma P‐tau231, that is, the groundbreaking research mentioned above (Ashton, Pascoal, et al, 2021). Taken together, it seems that the 5 year time span considered in our study allows for a comprehensive selection of studies with greater retrieval efficiency.…”

Section: Discussionmentioning

confidence: 99%

“…The less invasive and cheaper diagnostic techniques are being more commonly required to provide confirmatory evidence of underlying AD pathophysiology. Until relatively recently, our scientific advances in relation to the high‐sensitivity assays opened the opportunity to extend the use of fluid biomarkers to peripheral blood (Teunissen et al, 2022) and a panel of well‐validated blood biomarkers ensued, such as Aβ42/40 ratio (Xu et al, 2022), neurofibrillary light chain (NfL) (Bornhorst et al, 2022) and the newly identified different hyper‐phosphorylated tau (P‐tau) isoforms (Chen et al, 2022). NfL, a robustly increased biomarker in AD (Ashton et al, 2019; Mattsson et al, 2017), is also increased in other neurodegenerative disorders (Ashton, Janelidze, et al, 2021) and upon acute neurological injury (Wihersaari et al, 2021) owing to its characteristic of detecting axonal injury (Khalil et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

The performance of plasma phosphorylated tau231 in detecting Alzheimer's disease: A systematic review with meta‐analysis

Chang

Zhao

Dong

2023

Eur J of Neuroscience

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Cerebrospinal fluid (CSF) phosphorylated tau231 (P‐tau231) is associated with neuropathological outcomes of Alzheimer's disease (AD). The invasive access of cerebrospinal fluid has greatly stimulated interest in the identification of blood‐based P‐tau231, and the recent advent of single‐molecule array assay for the quantification of plasma P‐tau231 may provide a turning point to evaluate the usefulness of P‐tau231 as an AD‐related biomarker. Yet, in the plasma P‐tau231 literature, findings with regard to its diagnostic utility have been inconsistent, and thus, we aimed to statistically investigate the potential of plasma P‐tau231 in the context of AD via meta‐analysis. Publications on plasma P‐tau231 were systematically retrieved from PubMed, EMBASE, the Cochrane library and Web of Science databases. A total of 10 studies covering 2007 participants were included, and we conducted random‐effect or fixed‐effect meta‐analysis, sensitivity analysis and publication bias analysis using the STATA SE 14.0 software. According to our quantitative integration, plasma P‐tau231 increased from cognitively unimpaired (CU) populations to mild cognitive impairment to AD and showed significant changes in pairwise comparisons of AD, mild cognitive impairment and CU. Plasma P‐tau231 level was significantly higher in CU controls with positive amyloid‐β (Aβ) status compared with Aβ‐negative CU group. Additionally, the excellent diagnostic accuracy of plasma P‐tau231 for asymptomatic Aβ pathology was verified by the pooled value of area under the receiver operating characteristic curves (standard mean difference [95% confidence interval]: .75 [.69, .81], P < 0.00001). Overall, the increased plasma P‐tau231 concentrations were found in relation to the early development and progression of AD.

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“…Ultrasensitive blood tests predicting AD pathologies, amyloid‐β, and tau, in the brain have shown potential for both diagnostic and prognostic clinical application. 3 , 4 , 5 , 6 , 7 Among the most promising blood‐based biomarkers are plasma phosphorylated tau 181 (p‐tau181) 8 , 9 and phosphorylated tau 231 (p‐tau231). 10 Other plasma biomarkers that might aid future diagnostics of AD are plasma glial fibrillary acidic protein (GFAP), 11 plasma amyloid‐β 42 to amyloid‐β 40 ratio (Aβ42/Aβ40 ratio), 12 and plasma neurofilament light (NfL).…”

Section: Introductionmentioning

confidence: 99%

“…Ultrasensitive blood tests predicting AD pathologies, amyloid‐β, and tau, in the brain have shown potential for both diagnostic and prognostic clinical application 3–7 . Among the most promising blood‐based biomarkers are plasma phosphorylated tau 181 (p‐tau181) 8,9 and phosphorylated tau 231 (p‐tau231) 10 .…”

Section: Introductionmentioning

confidence: 99%

Preanalytical stability of plasma biomarkers for Alzheimer's disease pathology

Sunde

Alsnes

Aarsland

et al. 2023

Alz & Dem Diag Ass & Dis Mo

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Introduction Plasma tests have demonstrated high diagnostic accuracy for identifying Alzheimer's disease pathology. To facilitate the transition to clinical utility, we assessed whether plasma storage duration and temperature affect the biomarker concentrations. Methods Plasma samples from 13 participants were stored at +4°C and +18°C. Concentrations of six biomarkers were measured after 2, 4, 6, 8, 10, and 24 h by single molecule array assays. Results Phosphorylated tau 181 (p‐tau181), phosphorylated tau 231 (p‐tau231), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) concentrations were unchanged both when stored at +4°C and +18°C. Amyloid‐β 40 (Aβ40) and amyloid‐β 42 (Aβ42) concentrations were stable for 24 h at +4°C but declined when stored at +18°C for longer than 6 h. This decline did not affect the Aβ42/Aβ40 ratio. Discussion Plasma samples can be stored for 24 h at +4°C or +18°C and result in valid assay results for p‐tau181, p‐tau231, Aβ42/Aβ40 ratio, GFAP, and NfL. HIGHLIGHTS Plasma samples were stored for 24 h at +4°C and +18°C, mimicking clinical practice. Concentrations for Alzheimer's disease biomarkers were measured at six time‐points. p‐tau181, p‐tau231, NfL, and GFAP concentrations were unchanged during the experiment. Storage at +18°C affected Aβ40 and Aβ42 concentrations while storage at +4°C did not. The Aβ42/Aβ40 ratio was unaffected. These plasma tests seem suitable for use in general practice.

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Plasma tau proteins for the diagnosis of mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis

Cited by 11 publications

References 39 publications

Differential diagnosis of mild cognitive impairment of Alzheimer’s disease by Simoa p-tau181 measurements with matching plasma and CSF

Differential diagnosis of mild cognitive impairment of Alzheimer’s disease by Simoa p-tau181 measurements with matching plasma and CSF

The performance of plasma phosphorylated tau231 in detecting Alzheimer's disease: A systematic review with meta‐analysis

Preanalytical stability of plasma biomarkers for Alzheimer's disease pathology

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