Data origin and single-nucleus RNA velocity estimation
Single nucleus RNA-seq data was obtained from the prefrontal cortex of 48 postmortem human brain samples1 (Sects. “Methods”, “Dataset-1”). Twenty-four of these individuals had no or low β-amyloid burden or other pathologies (control). The remaining twenty-four presented mild to severe AD-pathology (amyloid burden, neurofibrillary tangles, global pathology, and cognitive impairment). After pre-processing, 65,422 snRNA-seq profiles with 16,844 transcripts (corresponding to 16,829 unique genes) were obtained. A predefined cluster list1 was used to annotate and assign the cells to six different types: excitatory neurons, inhibitory neurons, astrocytes, microglia, oligodendrocytes, and oligodendrocyte progenitor cells (Fig. 1a).