Browsing by Author "Cicognola, Claudia"

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    Comparing the Clinical Utility and Diagnostic Performance of CSF P-Tau181, P-Tau217, and P-Tau231 Assays
    (Wolters Kluwer, 2021) Leuzy, Antoine; Janelidze, Shorena; Mattsson-Carlgren, Niklas; Palmqvist, Sebastian; Jacobs, Dirk; Cicognola, Claudia; Stomrud, Erik; Vanmechelen, Eugeen; Dage, Jeffrey L.; Hansson, Oskar; Neurology, School of Medicine
    Background and objectives: Phosphorylated tau (p-tau) in CSF is considered an important biomarker in Alzheimer disease (AD) and has been incorporated in recent diagnostic criteria. Several variants exist, including p-tau at threonines 181 (p-tau181), 217 (p-tau217), and 231 (p-tau231). However, no studies have compared their diagnostic performance or association to β-amyloid (Aβ) and tau-PET. Understanding which p-tau variant to use remains an important yet answered question. We aimed to compare the diagnostic accuracy of p-tau181, p-tau217, and p-tau231 in CSF for AD and their association with Aβ and tau-PET. Methods: A total of 629 participants in the Swedish BioFINDER-2 study were included (cognitively unimpaired, n = 334; Aβ-positive mild cognitive impairment, n = 84; AD dementia, n = 119; and non-AD disorders, n = 92). In addition to p-tau181 and p-tau217 measured using assays with the same detector antibodies from Eli Lilly (p-tau181Lilly, p-tau217Lilly) and p-tau231, we also included p-tau181 measurements from 2 commonly used assays (Innotest and Elecsys). Results: Although all p-tau variants increased across the AD continuum, p-tau217Lilly showed the greatest dynamic range (13-fold increase vs 1.9-5.4-fold increase for other p-tau variants for AD dementia vs non-AD). P-Tau217Lilly showed stronger correlations with Aβ- and tau-PET (p < 0.0001). P-Tau217Lilly exhibited higher accuracy than other p-tau variants for separating AD dementia from non-AD (area under the curve [AUC], 0.98 vs 0.88 [p < 0.0001] - 0.96 [p < 0.05]) and for identifying Aβ-PET (AUC, 0.86 vs 0.74 [p < 0.0001] and 0.83 [p < 0.001]) and tau-PET positivity (AUC, 0.94 vs 0.80-0.92, p < 0.0001). Finally, p-Tau181Lilly generally performed better than the other p-tau181 assays (e.g., AD dementia vs non-AD, AUC, 0.96 vs 0.88 [p-tau181Innotest] and 0.89 [p-tau181Elecsys]; p < 0.0001). Discussion: CSF p-tau217Lilly seems to be more useful than other included p-tau assays in the workup of AD. Varied results across p-tau181 assays highlights the importance of anti-tau antibodies for biomarker performance. Classification of evidence: This study provides Class II evidence that p-tau217 provides higher diagnostic accuracy for diagnosis of AD dementia than p-tau181 or p-tau231.
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    Correction: Diagnostic and prognostic performance to detect Alzheimer's disease and clinical progression of a novel assay for plasma p-tau217
    (BMC, 2022-06-13) Groot, Colin; Cicognola, Claudia; Bali, Divya; Triana‑Baltzer, Gallen; Dage, Jeffrey L.; Pontecorvo, Michael J.; Kolb, Hartmuth C.; Ossenkoppele, Rik; Janelidze, Shorena; Hansson, Oskar; Neurology, School of Medicine
    Erratum for: Diagnostic and prognostic performance to detect Alzheimer's disease and clinical progression of a novel assay for plasma p-tau217. Groot C, Cicognola C, Bali D, Triana-Baltzer G, Dage JL, Pontecorvo MJ, Kolb HC, Ossenkoppele R, Janelidze S, Hansson O. Alzheimers Res Ther. 2022 May 14;14(1):67. doi: 10.1186/s13195-022-01005-8. PMID: 35568889
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    Diagnostic and prognostic performance to detect Alzheimer's disease and clinical progression of a novel assay for plasma p-tau217
    (BMC, 2022-05-14) Groot, Colin; Cicognola, Claudia; Bali, Divya; Triana‑Baltzer, Gallen; Dage, Jeffrey L.; Pontecorvo, Michael J.; Kolb, Hartmuth C.; Osssenkoppele, Rik; Janelidze, Shorena; Hansson, Oskar; Neurology, School of Medicine
    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-tau217Lilly, 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-tau217Lilly AUC = 0.89), distinguishing MCI from controls (plasma p-tau217+Janssen AUC = 0.91 vs plasma p-tau217Lilly AUC = 0.91), and predicting future conversion from MCI to AD dementia (plasma p-tau217+Janssen AUC = 0.88 vs p-tau217Lilly AUC = 0.89). Both assays were similarly related to baseline (plasma p-tau217+Janssen rho = -0.39 vs p-tau217Lilly rho = -0.35), and annual change in MMSE scores (plasma p-tau217+Janssenr = -0.45 vs p-tau217Lillyr = -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-tau217Lilly 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-tau217Lilly assay.