Browsing by Author "Grau-Rivera, Oriol"

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    Associations of 18F‐RO‐948 Tau PET with Fluid AD Biomarkers, Centiloid, and Cognition in the Early AD Continuum
    (Wiley, 2025-01-09) Shekari, Mahnaz; González Escalante, Armand; Milà-Alomà, Marta; Falcon, Carles; López-Martos, David; Sánchez-Benavides, Gonzalo; Brugulat-Serrat, Anna; Niñerola-Baizán, Aida; Ashton, Nicholas J.; Karikari, Thomas K.; Lantero Rodriguez, Juan; Snellman, Anniina; Day, Theresa A.; Dage, Jeffrey L.; Ortiz-Romero, Paula; Tonietto, Matteo; Borroni, Edilio; Klein, Gregory; Kollmorgen, Gwendlyn; Quijano-Rubio, Clara; Vanmechelen, Eugeen; Minguillón, Carolina; Fauria, Karine; Perissinotti, Andrés; Molinuevo, Jose Luis; Zetterberg, Henrik; Blennow, Kaj; Grau-Rivera, Oriol; Suárez-Calvet, Marc; Gispert, Juan Domingo; Neurology, School of Medicine
    Background: Fluid biomarkers provide a convenient way to predict AD pathophysiology. However, few studies have focused on determining associations with tau neurofibrillary tangle pathology in the early preclinical AD continuum, relevant to prevention strategies. Methods: Ninety‐nine cognitively unimpaired individuals from the ALFA+ cohort with valid 18F‐RO‐948 and 18F‐flutemetamol PET, T1‐weighted MRI, cognition, CSF, and plasma biomarkers were included. Participants were initially categorized into AT stages using CSF‐based pre‐established cut‐off values [1]. Regional SUVR of 18F‐RO‐948 PET was calculated in entorhinal(BraakI/II), limbic(BraakIII/IV), and neocortical(BraakV/VI) regions using the inferior cerebellum as reference region as well as with the CenTAURz. Regional positivity thresholds per Braak stage were calculated as the median+2SD of the CSF A‐T‐ group. Amyloid PET was quantified using Centiloids. Pearson correlations were calculated between regional 18F‐RO‐948 SUVRs and AD biomarkers. ROC analyses adjusted for age, sex, and APOE‐ε4 performed to evaluate the capacity of biomarkers in predicting BraakI/IIPositive. Four progressive PET‐derived AT groups were defined using Centiloid and tau PET positivity cut‐offs (A‐T‐, AGZT‐, A+T‐ and A+T+; with A‐ CL<12, 12≤AGZ<38 and A+ CL≥38 [2], and T+ BraakI/II>1.35) and between‐stage differences in z‐scored biomarkers evaluated using a Kruskal‐Wallis tests. Results: Table 1 shows demographic information of participants. Nine(9.09%) participants were BraakI/IIPositive, seven(7.07%) BraakIII/IVPositive and one(1.01%) BraakV/VIPositive. Two BraakIII/IVPositive participants were BraakI/IINegative, deviating from the Braak hierarchical model. CSF biomarker correlations with BraakI/II SUVR (Figure 1‐A) ranged from r=0.24(ttau) to r=0.57(ptau217) and plasma (Figure 1‐B) from r=0.30(ptau217) to r=0.49(ptau181). Correlations survived adding age+sex+APOE‐ε4 in the model (Figure 1‐C&D). CSF ptau181/Aβ42, ptau217 and ptau205 showed an AUC≥0.93 to predict BraakI/IIPositive, and plasma ptau181, ptau181/Aβ42 and ptau217 had an AUC≥0.84. Centiloid positivity threshold for BraakI/IIPositive was 38.14CL. Plasma ptau181, ptau181/Aβ42, and CSF ptau205, ptau217, and ptau235 reached a mean z‐score>2 for the PET‐derived A+T+ group (Figure 2) which was associated with lower cognitive scores for executive function (p=0.03), attention (p=0.05), and the PACC (p=0.01). Conclusion: 18F‐RO‐948 PET conformed to the Braak hierarchical model for most tau‐positive participants. Fluid AD biomarkers showed moderate associations with tau PET SUVR. Plasma biomarkers showed good capacity to predict BraakI/IIPositive and track fibrillary amyloid and tau pathological changes in the early preclinical AD continuum.
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    Plasma and CSF biomarkers in a memory clinic: Head-to-head comparison of phosphorylated tau immunoassays
    (Wiley, 2023) Ashton, Nicholas J.; Puig-Pijoan, Albert; Milà-Alomà, Marta; Fernández-Lebrero, Aida; García-Escobar, Greta; González-Ortiz, Fernándo; Kac, Przemysław R.; Brum, Wagner S.; Benedet, Andréa L.; Lantero-Rodriguez, Juan; Day, Theresa A.; Vanbrabant, Jeroen; Stoops, Erik; Vanmechelen, Eugeen; Triana-Baltzer, Gallen; Moughadam, Setareh; Kolb, Hartmuth; Ortiz-Romero, Paula; Karikari, Thomas K.; Minguillon, Carolina; Hernández Sánchez, Juan José; Navalpotro-Gómez, Irene; Grau-Rivera, Oriol; Manero, Rosa María; Puente-Periz, Víctor; de la Torre, Rafael; Roquer, Jaume; Dage, Jeff L.; Zetterberg, Henrik; Blennow, Kaj; Suárez-Calvet, Marc; Neurology, School of Medicine
    Introduction: Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences. Methods: In the BIODEGMAR study, 197 participants presenting with cognitive complaints were classified into an Alzheimer's disease (AD) or a non-AD cerebrospinal fluid (CSF) profile group, according to their amyloid beta 42/ phosphorylated tau (Aβ42/p-tau) ratio. We performed a head-to-head comparison of nine plasma and nine CSF tau immunoassays and determined their accuracy to discriminate abnormal CSF Aβ42/p-tau ratio. Results: All studied plasma tau biomarkers were significantly higher in the AD CSF profile group compared to the non-AD CSF profile group and significantly discriminated abnormal CSF Aβ42/p-tau ratio. For plasma p-tau biomarkers, the higher discrimination accuracy was shown by Janssen p-tau217 (r = 0.76; area under the curve [AUC] = 0.96), ADx p-tau181 (r = 0.73; AUC = 0.94), and Lilly p-tau217 (r = 0.73; AUC = 0.94). Discussion: Several plasma p-tau biomarkers can be used in a specialized memory clinic as a stand-alone biomarker to detect biologically-defined AD. Highlights: Patients with an Alzheimer's disease cerebrospinal fluid (AD CSF) profile have higher plasma phosphorylated tau (p-tau) levels than the non-AD CSF profile group. All plasma p-tau biomarkers significantly discriminate patients with an AD CSF profile from the non-AD CSF profile group. Janssen p-tau217, ADx p-tau181, and Lilly p-tau217 in plasma show the highest accuracy to detect biologically defined AD. Janssen p-tau217, ADx p-tau181, Lilly p-tau217, Lilly p-tau181, and UGot p-tau231 in plasma show performances that are comparable to their CSF counterparts.