The vulnerability of specific brain regions to Alzheimer disease (AD) pathology is associated with expression profiles of AD susceptibility genes, according to new research. To characterize regional vulnerability, Yu et al. compared tau and amyloid-β (Aβ) PET imaging data from people with cognitive impairment, including AD and mild cognitive impairment, and cognitively unimpaired individuals. Transcriptomic analysis revealed spatial associations between the gene-expression profiles of 45 AD susceptibility genes and regional vulnerability to tau or Aβ deposition. APOE and MAPT were among the genes most strongly associated with tau pathology, whereas TMEM106B (which encodes a lysosomal membrane protein) and CNTNAP2 (which is involved in neuroglia interactions) showed the strongest association with Aβ pathology.