Single-nucleus RNA velocity reveals critical synaptic and cell-cycle dysregulations in neuropathologically confirmed Alzheimer’s disease

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).

Single-nucleus RNA-seq of the prefrontal cortex of 48 individuals across the Alzheimer’s…