CSF p-tau231: A biomarker for early preclinical Alzheimer?

Suárez‐Calvet, Marc

doi:10.1016/j.ebiom.2022.103936

Cited by 5 publications

(3 citation statements)

References 10 publications

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“…Fosforylace tau proteinu v mozku je pokládána za dynamický proces. Studium vybraných fosforylovaných tau proteinů naznačuje, že jejich koncentrace odrážejí časné poruchy v metabolismu tau proteinu ještě v preklinickém stádiu AN, pravděpodobně jako reakci na počáteční patologické změny β-amyloidu 51 .…”

Section: Fosforylované Formy Tau Proteinuunclassified

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Tau Protein in Biological Fluids and Its Clinical Value

Fialová,

Nosková,

Zima

2024

Chem. Listy

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The tau protein is one of the neurocytoskeletal proteins that participate in the pathogenesis of serious neurological diseases, especially Alzheimer's disease. The tau protein is characterized by considerable structural variability, which is reflected in the existence of its numerous proteoforms. This review aims to provide brief information on the structure of tau protein and its proteoforms, which seem promising biomarkers for clinical use. Biological fluids, suitable for laboratory examination in clinical practice, i.e., cerebrospinal fluid and blood (plasma/serum), are discussed. Total tau protein and its phosphorylated forms (mainly the pT181-tau protein, phosphorylated at the threonine residue 181) have already found clinical application in diagnosis of Alzheimer's disease.

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Section: Fosforylované Formy Tau Proteinuunclassified

“…K dalším perspektivním fosforylovaným tau proteinům v MMM můžeme zařadit p-tau proteiny fosforylované na aminokyselinovém zbytku threoninu 217 (pT217-tau) a 231 (pT231-tau) 51,53,54 . Oba tyto fosforylované tau proteiny byly označeny za specifičtější biomarkery pro AN než pT181-tau protein.…”

Section: Fosforylované Formy Tau Proteinuunclassified

Tau Protein in Biological Fluids and Its Clinical Value

Fialová,

Nosková,

Zima

2024

Chem. Listy

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“…Thanks to its direct connection with central nervous system (CNS), cerebrospinal fluid (CSF) is considered as a primary matrix of interest for detection of AD biomarkers. The main biomarkers already implemented in the AD diagnostic process are betaamyloid peptides (Aβ42 , Aβ40 , and Aβ42/Aβ40 ratio), total tau (t-tau), and different forms of phosphorylated tau (primarily, p-tau181, and to some extent, p-tau231 and p-tau217) [5,6].…”

Section: Introductionmentioning

confidence: 99%

Targeting multiphosphorylated tau: technical and clinical validation of a new Simoa® assay for CSF and plasma detection of tau simultaneously phosphorylated at T181 and T231

Wojdała

Bellomo

Gaetani

et al. 2023

Preprint

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Background and Objectives: Different forms of phosphorylated tau (p-tau) have shown high potential as Alzheimer′s Disease (AD) biomarkers in both cerebrospinal fluid (CSF) and plasma. Hence, we hypothesized that tau peptides showing concomitant phosphorylation at two different sites may provide an increased diagnostic value. We therefore developed and validated a new Simoa® immunoassay detecting tau simultaneously phosphorylated at T181 and T231 (C231D181) in cerebrospinal fluid (CSF) and plasma. Methods: Technical validation of the C231D181 Simoa® assay included standard curve development, assessment of antibodies cross-reactivity, dilutional linearity, sensitivity, as well as intra- and inter-assay precision. Subsequently, we measured CSF C231D181, p-tau181, and p-tau231 in two cohorts: discovery (MCI-AD n=21, AD dementia n=19, CTRL n=15) and validation (preclinical AD n=19, MCI-AD n=20, AD dementia n=16, frontotemporal dementia n=39, CTRL n=24). Additionally, in the discovery cohort, C231D181, p-tau181, and p-tau231 levels were measured in matched plasma samples. Results: Specificity of the assay was assessed using a synthetic peptide simultaneously phosphorylated at T181 and T231, while cross-reactivity was excluded with a mix of single-site phosphorylated peptides (T181 or T231). Both in discovery and validation cohorts, CSF C231D181, p-tau181, and p-tau231 levels were significantly elevated in all AD groups vs. CTRL. As assessed in discovery cohort, plasma p-tau231 and p-tau181 levels enabled effective discrimination of AD continuum groups from CTRL (AUC plasma p-tau231: CTRL vs. MCI-AD=0.925, CTRL vs. AD-dem=0.947; AUC plasma p-tau181: CTRL vs. MCI-AD=0.877, CTRL vs. AD-dem=0.943) while plasma C231D181 did not change among clinical groups. Discussion: A new ultrasensitive immunoassay detecting tau simultaneously phosphorylated at T181 and T231 was developed and validated. While we found this phosphorylated tau form to be significantly elevated across the AD continuum in CSF, in plasma it did not show changes among the diagnostic groups. The differences between CSF and plasma suggest matrix-specific protein processing. Our findings support evidence for qualitative and quantitative importance of tau phosphorylation across AD continuum and warrant further investigation, including assessment of tau simultaneously phosphorylated at multiple sites.

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