https://www.selleckchem.com/products/suzetrigine.html Recently, the focus of Alzheimer's disease (AD) research has shifted from the clinical stage to the preclinical stage. We, therefore, aimed to develop a cognitive composite score that can detect the subtle cognitive differences between the amyloid positive (Aβ+) and negative (Aβ-) status in cognitively normal (CN) participants. A total of 423 CN participants with Aβ positron emission tomography images were recruited. The multiple-indicators multiple-causes model found the latent mean difference between the Aβ+ and Aβ- groups in the domains of verbal memory, visual memory, and executive functions. The multivariate analysis of covariance (MANCOVA) showed that the Aβ+ group performed worse in tests related to the verbal and visual delayed recall, semantic verbal fluency, and inhibition of cognitive inference within the three cognitive domains. The Preclinical Amyloid Sensitive Composite (PASC) model we developed using the result of MANCOVA and the MMSE presented a good fit with the data. The accuracy of the PASC score when applied with age, sex, education, and APOE ε4 for distinguishing between Aβ+ and Aβ- was adequate (AUC = 0.764; 95% CI = 0.667-0.860) in the external validation set (N = 179). We conclude that the PASC can eventually contribute to facilitating more prevention trials in preclinical AD.Natural mitochondrial DNA (mtDNA) mutations enable the inference of clonal relationships among cells. mtDNA can be profiled along with measures of cell state, but has not yet been combined with the massively parallel approaches needed to tackle the complexity of human tissue. Here, we introduce a high-throughput, droplet-based mitochondrial single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq), a method that combines high-confidence mtDNA mutation calling in thousands of single cells with their concomitant high-quality accessible chromatin profile. This enables the inference of mtDNA hete