Browsing by Author "Sánchez-Benavides, Gonzalo"
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Item 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 MedicineBackground: 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.Item Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer's disease(Springer Nature, 2022) Milà-Alomà, Marta; Ashton, Nicholas J.; Shekari, Mahnaz; Salvadó, Gemma; Ortiz-Romero, Paula; Montoliu-Gaya, Laia; Benedet, Andrea L.; Karikari, Thomas K.; Lantero-Rodriguez, Juan; Vanmechelen, Eugeen; Day, Theresa A.; González-Escalante, Armand; Sánchez-Benavides, Gonzalo; Minguillon, Carolina; Fauria, Karine; Molinuevo, José Luis; Dage, Jeffrey L.; Zetterberg, Henrik; Gispert, Juan Domingo; Suárez-Calvet, Marc; Blennow, Kaj; Neurology, School of MedicineBlood biomarkers indicating elevated amyloid-β (Aβ) pathology in preclinical Alzheimer's disease are needed to facilitate the initial screening process of participants in disease-modifying trials. Previous biofluid data suggest that phosphorylated tau231 (p-tau231) could indicate incipient Aβ pathology, but a comprehensive comparison with other putative blood biomarkers is lacking. In the ALFA+ cohort, all tested plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NfL and Aβ42/40) were significantly changed in preclinical Alzheimer's disease. However, plasma p-tau231 reached abnormal levels with the lowest Aβ burden. Plasma p-tau231 and p-tau217 had the strongest association with Aβ positron emission tomography (PET) retention in early accumulating regions and associated with longitudinal increases in Aβ PET uptake in individuals without overt Aβ pathology at baseline. In summary, plasma p-tau231 and p-tau217 better capture the earliest cerebral Aβ changes, before overt Aβ plaque pathology is present, and are promising blood biomarkers to enrich a preclinical population for Alzheimer's disease clinical trials.Item Publisher Correction: Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer's disease(Springer Nature, 2022) Milà-Alomà, Marta; Ashton, Nicholas J.; Shekari, Mahnaz; Salvadó, Gemma; Ortiz-Romero, Paula; Montoliu-Gaya, Laia; Benedet, Andrea L.; Karikari, Thomas K.; Lantero-Rodriguez, Juan; Vanmechelen, Eugeen; Day, Theresa A.; González-Escalante, Armand; Sánchez-Benavides, Gonzalo; Minguillon, Carolina; Fauria, Karine; Molinuevo, José Luis; Dage, Jeffrey L.; Zetterberg, Henrik; Gispert, Juan Domingo; Suárez-Calvet, Marc; Blennow, Kaj; Neurology, School of MedicineThis corrects the article "Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease" in Nat Med, volume 28 on page 1797.