Brain charts for the human lifespan have been recently proposed to build dynamic models of brain anatomy in normal aging and various neurological conditions. They offer new possibilities to quantify neuroanatomical changes from preclinical stages to death, where longitudinal MRI data are not available. In this study, we used brain charts to model the progression of brain atrophy in progressive supranuclear palsy – Richardson syndrome (PSPRS). We combined multiple datasets (n=8170 quality controlled MRI of healthy subjects from 22 cohorts covering the entire lifespan, and n=62 MRI of PSP-RS patients from the 4 Repeat Tauopathy Neuroimaging Initiative) to extrapolate lifetime volumetric models of healthy and PSP-RS brain structures. We then mapped in time and space the sequential divergence between healthy and PSP-RS charts. We found six major consecutive stages of atrophy progression: (i) ventral diencephalon (including subthalamic nuclei, substantia nigra, and red nuclei), (ii) pallidum, (iii) brainstem, striatum and amygdala, (iv) thalamus, (v) frontal lobe and (vi) occipital lobe. The three structures with most severe atrophy over time were the thalamus, followed by the pallidum and the brainstem. These results match the neuropathological staging of tauopathy progression in PSP-RS, where the pathology is supposed to start in the pallido-nigro-luysian system and spreads rostrally via the striatum and the amygdala to the cerebral cortex, and caudally to the brainstem. This study supports the use of brain charts for the human lifespan to study the progression of neurodegenerative diseases, especially in the absence of specific biomarkers as in PSP.< Leer menos