[18F]RO‐948 Tau PET Retention and Correlation with Fluid Tau Biomarkers in the Early AD Continuum. (20th December 2022)

• Record Type: Journal Article
• Authors: Shekari, Mahnaz; Milà‐Alomà, Marta; Falcon, Carles; Niñerola‐Baizán, Aida; Tonietto, Matteo; Borroni, Edilio; Klein, Gregory; Ashton, Nicholas J.; Karikari, Thomas K; Rodriguez, Juan Lantero; Snellman, Anniina; Ortiz‐Romero, Paula; Vanmechelen, Eugeen; Minguillón, Carolina; Fauria, Karine; Perissinotti, Andrés; Molinuevo, Jose Luis; Zetterberg, Henrik; Blennow, Kaj; Grau‐Rivera, Oriol; Suárez‐Calvet, Marc; Gispert, Juan Domingo
• Is Part Of: Alzheimer's & dementia. Volume 18(2022)Supplement 6
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-20
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.065900
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Tau positron emission tomography (PET) imaging enables the in vivo visualization of tau aggregates occurring during the progression of Alzheimer's disease (AD). Tau PET imaging is a promising biomarker for clinical diagnosis and tracking of disease progression. However, the sensitivity of tau PET in detecting early tau pathology within the early AD continuum and its association with fluid tau biomarkers remains to be established. Method: Forty‐seven cognitively unimpaired individuals from the ALFA+ cohort had [ 18 F]RO‐948 and [ 18 F]flutemetamol PET, T1‐weighted magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and plasma tau biomarkers available (Table1 ). CSF amyloid(A) and tau(T) positivity were defined using CSF Aß42/40 ratio and ptau181 measured by the exploratory NeuroToolKit and Elecsys® immunoassays, respectively, according to pre‐established thresholds (Milà‐Alomà et al ., 2020). Centiloid (CL) values were obtained from [ 18 F]flutemetamol PET scans using a validated pipeline. [ 18 F]RO‐948 uptake was measured in entorhinal (BraakI/II), limbic (BraakIII/IV), and neocortical (BraakV/VI) regions and normalized to the inferior cerebellum to render SUVR values. Regional positivity thresholds per Braak stage were calculated as the median plus two robust standard deviations. Associations between [ 18 F]RO‐948 SUVRs and fluid tau biomarkers were evaluated using Spearman's rho correlations. P‐values<0.05 were considered statistically significant. [ 18 F]RO‐948 SUVRs were modeled against CL values using the data‐driven robust LOWESS method. Result: In BraakI/II, 5 cases were considered to be positive, 3 in BraakIII/IV and 2 in BraakV/VI (see Table2 for thresholds), all of them being A+T+. Significant correlations with fluid biomarkers were observed in all Braak stages (Table3, Figure1 ). [ 18 F]RO‐948 SUVR in BraakI/II showed a linear trend with CL values and inflection points between 20 and 30 CLs were observed for all Braak stages (Figure2 ). Conclusion: A progressively lower number of [ 18 F]RO‐948 PET‐positive cases were detected for more advanced Braak stages as expected from neuropathological studies. [ 18 F]RO‐948 uptake started increasing around 20‐30 CLs and correlated with wet tau biomarkers in cognitively unimpaired individuals, suggesting that [ 18 F]RO‐948 PET can be more sensitive to initial tau pathology than previously thought. These preliminary findings demonstrate that the ALFA+ cohort is well‐suited to study early pathophysiological alterations in preclinical AD stages.