Frontiers in neuroscience
Regional tau burden tracks with lower microglial HLA class II transcription in the human brain
By Li F, Jin S, Wang P and 4 others.
Abstract
Background
Human leukocyte antigen class II (HLA-II) genes mark several microglial states in Alzheimer's disease, but it remains unclear how their average transcription relates to tau measured in the same brain region.
Methods
We used a locked 13-gene HLA-II panel selected by biological function, cross-cohort detection, and variance, without considering effect estimates. The primary analysis was conducted using the Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD): 361 donor-region observations from 79 donors across 6 cortical regions were modeled with within-donor pathology decomposition, region fixed effects, and a donor random intercept. A paired entorhinal-versus-somatosensory analysis in GSE160936 (11 donors) provided additional support for our findings. Sensitivity analyses addressed amyloid-β, RNA quality, neuronal-nuclei enrichment, microglial-state composition, published state annotations, alternative panels, region omission, and assay modality. Public human induced pluripotent stem cell (iPSC)-microglia data were used to provide a distinct tau-exposure context.