| 1. |
- Groot, Colin, et al.
(author)
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Diagnostic and prognostic performance to detect Alzheimer's disease and clinical progression of a novel assay for plasma p-tau217
- 2022
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In: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1, s. 1-12
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Journal article (peer-reviewed)abstract
- BACKGROUND: Recent advances in disease-modifying treatments highlight the need for accurately identifying individuals in early Alzheimer's disease (AD) stages and for monitoring of treatment effects. Plasma measurements of phosphorylated tau (p-tau) are a promising biomarker for AD, but different assays show varying diagnostic and prognostic accuracies. The objective of this study was to determine the clinical performance of a novel plasma p-tau217 (p-tau217) assay, p-tau217+ Janssen, and perform a head-to-head comparison to an established assay, plasma p-tau217 Lilly, within two independent cohorts . METHODS: The study consisted of two cohorts, cohort 1 (27 controls and 25 individuals with mild-cognitive impairment [MCI]) and cohort 2 including 147 individuals with MCI at baseline who were followed for an average of 4.92 (SD 2.09) years. Receiver operating characteristic analyses were used to assess the performance of both assays to detect amyloid-β status (+/-) in CSF, distinguish MCI from controls, and identify subjects who will convert from MCI to AD dementia. General linear and linear mixed-effects analyses were used to assess the associations between p-tau and baseline, and annual change in Mini-Mental State Examination (MMSE) scores. Spearman correlations were used to assess the associations between the two plasma measures, and Bland-Altmann plots were examined to assess the agreement between the assays. RESULTS: Both assays showed similar performance in detecting amyloid-β status in CSF (plasma p-tau217+ Janssen AUC = 0.91 vs plasma p-tau217 Lilly AUC = 0.89), distinguishing MCI from controls (plasma p-tau217+ Janssen AUC = 0.91 vs plasma p-tau217 Lilly AUC = 0.91), and predicting future conversion from MCI to AD dementia (plasma p-tau217+ Janssen AUC = 0.88 vs p-tau217 Lilly AUC = 0.89). Both assays were similarly related to baseline (plasma p-tau217+ Janssen rho = -0.39 vs p-tau217 Lilly rho = -0.35), and annual change in MMSE scores (plasma p-tau217+ Janssenr = -0.45 vs p-tau217 Lillyr = -0.41). Correlations between the two plasma measures were rho = 0.69, p < 0.001 in cohort 1 and rho = 0.70, p < 0.001 in cohort 2. Bland-Altmann plots revealed good agreement between plasma p-tau217+ Janssen and plasma p-tau217 Lilly in both cohorts (cohort 1, 51/52 [98%] within 95%CI; cohort 2, 139/147 [95%] within 95%CI). CONCLUSIONS: Taken together, our results indicate good diagnostic and prognostic performance of the plasma p-tau217+ Janssen assay, similar to the p-tau217 Lilly assay.
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| 2. |
- Janelidze, Shorena, et al.
(author)
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Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer’s disease
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD), reflecting abnormal tau metabolism in the brain. Here we investigate the performance of CSF p-tau217 as a biomarker of AD in comparison to p-tau181. In the Swedish BioFINDER cohort (n = 194), p-tau217 shows stronger correlations with the tau positron emission tomography (PET) tracer [18F]flortaucipir, and more accurately identifies individuals with abnormally increased [18F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with [18F]flortaucipir uptake. P-tau217 correlates better than p-tau181 with CSF and PET measures of neocortical amyloid-β burden and more accurately distinguishes AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [18F]flortaucipir are corroborated in an independent EXPEDITION3 trial cohort (n = 32). The main results are validated using a different p-tau217 immunoassay. These findings suggest that p-tau217 might be more useful than p-tau181 in the diagnostic work up of AD.
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| 3. |
- Janelidze, Shorena, et al.
(author)
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Head-to-head comparison of 10 plasma phospho-tau assays in prodromal Alzheimer's disease.
- 2023
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In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 146:4, s. 1592-1601
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Journal article (peer-reviewed)abstract
- Plasma phospho-tau (p-tau) species have emerged as the most promising blood-based biomarkers of Alzheimer's disease. Here, we performed a head-to-head comparison of p-tau181, p-tau217 and p-tau231 measured using 10 assays to detect abnormal brain amyloid-β status and predict future progression to Alzheimer's dementia. The study included 135 patients with baseline diagnosis of mild cognitive impairment (mean age 72.4 years; 60.7% women) who were followed for an average of 4.9 years. Seventy-one participants had abnormal Aβ-status (i.e., abnormal CSF Aβ42/40) at baseline; and 45 of these Aβ-positive participants progressed to Alzheimer's dementia during follow-up. P-tau concentrations were determined in baseline plasma and CSF. P-tau217 and p-tau181 were both measured using immunoassays developed by Lilly Research Laboratories (Lilly) and mass spectrometry assays developed at Washington University (WashU). P-tau217 was also analysed using Simoa immunoassay developed by Janssen Research and Development (Janss). P-tau181 was measured using Simoa immunoassay from ADxNeurosciences (ADx), Lumipulse immunoassay from Fujirebio (Fuji) and Splex immunoassay from Mesoscale Discovery (Splex). Both p-tau181 and p-tau231 were quantified using Simoa immunoassay developed at the University of Gothenburg (UGOT). We found that the mass spectrometry-based p-tau217 (p-tau217WashU) exhibited significantly better performance than all other plasma p-tau biomarkers when detecting abnormal Aβ status (AUC=0.947; pdiff<0.015) or progression to Alzheimer's dementia (AUC=0.932; pdiff<0.027). Among immunoassays, p-tau217Lilly had the highest AUCs (0.886-0.889), which was not significantly different from the AUCs of p-tau217Janss, p-tau181ADx and p-tau181WashU (AUCrange, 0.835-0.872; pdiff>0.09), but higher compared with AUC of p-tau231UGOT, p-tau181Lilly, p-tau181UGOT, p-tau181Fuji, and p-tau181Splex (AUCrange, 0.642-0.813; pdiff ≤0.029). Correlations between plasma and CSF values were strongest for p-tau217WashU (R=0.891) followed by p-tau217Lilly (R=0.755; pdiff=0.003 vs p-tau217WashU) and weak to moderate for the rest of the p-tau biomarkers (Rrange, 0.320-0.669). In conclusion, the findings suggest that among all tested plasma p-tau assays, mass spectrometry-based measures of p-tau217 perform best when identifying mild cognitive impairment patients with abnormal brain Aβ or those who will subsequently progress to Alzheimer's dementia. Several other assays (p-tau217Lilly, p-tau217Janss, p-tau181ADx, and p-tau181WashU) showed relatively high and consistent accuracy across both outcomes. The results further indicate that the highest performing assays have performance metrics that rival the gold standards of Aβ-PET and CSF. If further validated, our findings will have significant impacts in diagnosis, screening and treatment for Alzheimer's dementia in the future.
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| 4. |
- Sexton, Claire E., et al.
(author)
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Novel avenues of tau research
- 2024
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In: Alzheimer's and Dementia. - 1552-5260. ; 20:3, s. 2240-2261
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Research review (peer-reviewed)abstract
- INTRODUCTION: The pace of innovation has accelerated in virtually every area of tau research in just the past few years. METHODS: In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation. RESULTS: Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research. DISCUSSION: The virtual meeting provided an opportunity to foster cross-sector collaboration and partnerships as well as a forum for updating colleagues on research-advancing tools and programs that are steadily moving the field forward.
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