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. Competing Interest Statement The authors have declared no competing interest. Footnotes Author order adjusted: Sarah Jaekel as last author Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.