Fig. 1. LC integrity predicts tau spreading in subsequent years.
a, A schematic representation of the neuroimaging analysis between LC integrity (inverted signal) and tau PET images (brain mesh rendered using SurfIce; https://www.nitrc.org/projects/surfice/) (left). Baseline LC integrity (inverted signal) was associated with longitudinal bilateral hippocampus and left amygdala tau (P < 0.05 cluster-corrected for multiple comparisons) using whole-brain voxel-wise level GLM analysis (n = 77 independent individuals) (right). The brain projection shows one-tailed results (z-score > 1.64; the color bar shows the z-statistics; cooler colors represent a stronger association). The results are displayed on sagittal, coronal and axial brain views using FSLeyes (FSL, FMRIB). b, Each distribution represents the longitudinal relationship between LC integrity (inverted signal) and the tau signal from the voxels within the left or the right MTL clusters surviving the multiple comparisons correction from the previous analysis. These distributions were compared using pairwise t-statistics (left cluster, n = 186 voxels; right cluster, n = 77 voxels). Distributions in red correspond to the tau pathway from baseline LC integrity to follow-up MTL tau; distributions in gray correspond to the pathway from baseline MTL tau to follow-up LC integrity. c, Using ex vivo data (n = 160 independent individuals), the proportion of low versus high tangle density in LC was tested against the proportion of having low versus high hippocampal tangles (for calculation of the threshold, see Methods; blue dots represent unimpaired participants and red dots represent impaired (MCI and AD) participants). L, left; R, right.