Brain Region-Specific Oligodendrocyte States Highlight Mitochondrial Gene Upregulation and Loss of Canonical Identity Signatures in Alzheimer’s Disease

Abstract Oligodendrocyte dysfunction and heterogeneity are emerging as key contributors to Alzheimer’s disease (AD) pathology, though cellular mechanisms remain unclear. Using single-nucleus RNA sequencing across three cortical regions from the same individuals, we identified region- and disease-specific transcriptomic changes, including increased mitochondrial genes and loss of cell type signatures. These results highlight the importance of biologically-informed quality control and underscore the value of multi-regional analysis for understanding AD pathogenesis and progression.