Longitudinal Associations of Blood Phosphorylated Tau181 and Neurofilament Light Chain With Neurodegeneration in Alzheimer Disease

Moscoso, Alexis; Grothe, Michel J.; Ashton, Nicholas J.; Karikari, Thomas K.; Rodrı́guez, Juan Lantero; Snellman, Anniina; Suárez‐Calvet, Marc; Blennow, Kaj; Zetterberg, Henrik; Schöll, Michael; Initiative, Alzheimer’s Disease Neuroimaging

doi:10.1001/jamaneurol.2020.4986

Cited by 158 publications

(146 citation statements)

References 56 publications

(82 reference statements)

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“…Additionally, Plasma pThr181 has diagnostic value and can differentiate AD from other neurodegenerative diseases such as FTLD with 70–80% sensitivity and specificity [ 128 ]. A longitudinal prospective study tracked a cohort of 1113 participants with follow up 8 years later and found that plasma pThr181 tau levels is associated with progressive decline in cognitive symptoms and brain atrophy [ 130 ]. This association was also found in patients with MCI, suggesting that plasma pThr181 could be an early predictor of neurodegeneration and cognitive decline.…”

Section: Main Textmentioning

confidence: 99%

“Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies

Xia

Prokop

Giasson

2021

Mol Neurodegeneration

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Phosphorylation is one of the most prevalent post-translational modifications found in aggregated tau isolated from Alzheimer’s disease (AD) patient brains. In tauopathies like AD, increased phosphorylation or hyperphosphorylation can contribute to microtubule dysfunction and is associated with tau aggregation. In this review, we provide an overview of the structure and functions of tau protein as well as the physiologic roles of tau phosphorylation. We also extensively survey tau phosphorylation sites identified in brain tissue and cerebrospinal fluid from AD patients compared to age-matched healthy controls, which may serve as disease-specific biomarkers. Recently, new assays have been developed to measure minute amounts of specific forms of phosphorylated tau in both cerebrospinal fluid and plasma, which could potentially be useful for aiding clinical diagnosis and monitoring disease progression. Additionally, multiple therapies targeting phosphorylated tau are in various stages of clinical trials including kinase inhibitors, phosphatase activators, and tau immunotherapy. With promising early results, therapies that target phosphorylated tau could be useful at slowing tau hyperphosphorylation and aggregation in AD and other tauopathies.

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Section: Main Textmentioning

confidence: 99%

“Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies

Xia

Prokop

Giasson

2021

Mol Neurodegeneration

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show abstract

“…Similarly, O'Connor et al [145] observed, in their longitudinal study of FAD, that plasma p-tau 181 concentrations were higher in mutation carriers than non-carriers from 16 years prior to estimated symptom onset. Furthermore, Moscoso et al [146] have recently shown that longitudinal changes in plasma p-tau 181 are associated with longitudinal neurodegeneration in AD-specific brain regions, as measured by FDG-PET and grey matter volume. Together, this evidence suggests plasma p-tau 181 poses a promising blood-based biomarker for both AD diagnosis and for patient recruitment into clinical trials.…”

Section: P-tau181 217 and 231 As Tau Biomarkers In Bloodmentioning

confidence: 99%

Transitioning from cerebrospinal fluid to blood tests to facilitate diagnosis and disease monitoring in Alzheimer's disease

et al. 2021

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Alzheimer's disease (AD) is increasingly prevalent worldwide, and disease-modifying treatments may soon be at hand; hence, now, more than ever, there is a need to develop techniques that allow earlier and more secure diagnosis. Current biomarker-based guidelines for AD diagnosis, which have replaced the historical symptom-based guidelines, rely heavily on neuroimaging and cerebrospinal fluid (CSF) sampling. While these have greatly improved the diagnostic accuracy of AD pathophysiology, they are less practical for application in primary care, population-based and epidemiological settings, or where resources are limited. In contrast, blood is a more accessible and cost-effective source of biomarkers in AD. In this review paper, using the recently proposed amyloid, tau and neurodegeneration [AT(N)] criteria as a framework towards a biological definition of AD, we discuss recent advances in biofluid-based biomarkers, with a particular emphasis on those with potential to be translated into blood-based biomarkers. We provide an overview of the research conducted both in CSF and in blood to draw conclusions on biomarkers that show promise. Given the evidence collated in this review, plasma neurofilament light chain (N) and phosphorylated tau (p-tau; T) show particular potential for translation into clinical practice. However, p-tau requires more comparisons to be conducted between its various epitopes before conclusions can be made as to which one most robustly differentiates AD from non-AD dementias. Plasma amyloid beta (A) would prove invaluable as an early screening modality, but it requires very precise tests and robust preanalytical protocols.

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“…Nine studies that used Simoa or MSD methods were included for the analysis of normal range of plasma ptau181. Six publications, reporting seven cohorts, were retrieved using the Simoa technology [45,[84][85][86][87][88], including 1424 healthy subjects. The ES for plasma ptau181 levels in healthy populations was 11.18 pg/ml (95% CI 9.68-12.68, I 2 = 95.9%, P < 0.0001, Fig.…”

Section: Study Inclusions and Quality Assessmentmentioning

confidence: 99%

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

Ding

Zhang

Jiang

et al. 2021

Transl Neurodegener

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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.

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Longitudinal Associations of Blood Phosphorylated Tau181 and Neurofilament Light Chain With Neurodegeneration in Alzheimer Disease

Cited by 158 publications

References 56 publications

“Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies

“Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies

Transitioning from cerebrospinal fluid to blood tests to facilitate diagnosis and disease monitoring in Alzheimer's disease

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

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