Here, we use a deep learning method to analyse RNA-seq data from 1114 brain donors from the Accelerating Medicines Project for Alzheimer’s Disease consortium to characterize post-mortem brain transcriptome signatures associated with amyloid-β plaque, tau neurofibrillary tangles and clinical severity in multiple Alzheimer’s disease dementia populations. The gene discussed is MAPT; the disease is early-onset autosomal dominant Alzheimer disease.