Multi-region m⁶A epitranscriptome profiling of the human brain reveals spatial and temporal variation and enrichment of disease-associated loci

N⁶-methyladenosine (m⁶A) is a major RNA modification in the brain, regulating neural processes and contributing to disease mechanisms. Despite its importance, regional, age-specific and sex-specific m⁶A patterns in the human brain are still poorly described. Here, we profiled m⁶A mRNA modifications in five human brain regions (Brodmann areas 9 and 24, and the caudate, hippocampus and thalamus) across 25 individuals of different ages, ranging from 0 to 71 years old. We uncovered widespread regional differences for m⁶A patterns in the brain, notably in disease-risk genes, while age-related changes were most prominent in the prefrontal cortex. Integrating m⁶A data with whole-genome sequencing revealed that m⁶A modifications are associated with disease-related genetic loci. Our work identifies the spatial and temporal variation in m⁶A modifications and suggests how they could contribute to neurological disorders.