A shared disease-associated oligodendrocyte signature among multiple CNS pathologies

We identified an oligodendrocyte signature associated with brain pathology in the 5xFAD model of amyloidosis, which we termed disease-associated oligodendrocytes. This signature was found to be shared by oligodendrocytes across pathologies. Alzheimer's disease (AD) is a complex neurodegenerative disease, perturbing neuronal and non-neuronal cell populations. In this study, using single-cell transcriptomics, we mapped all non-immune, non-neuronal cell populations in wild-type and AD model (5xFAD) mouse brains. We identified an oligodendrocyte state that increased in association with brain pathology, which we termed disease-associated oligodendrocytes (DOLs). In a murine model of amyloidosis, DOLs appear long after plaque accumulation, and amyloid-beta (A beta) alone was not sufficient to induce the DOL signature in vitro. DOLs could be identified in a mouse model of tauopathy and in other murine neurodegenerative and autoimmune inflammatory conditions, suggesting a common response to severe pathological conditions. Using quantitative spatial analysis of mouse and postmortem human brain tissues, we found that oligodendrocytes expressing a key DOL marker (SERPINA3N/SERPINA3 accordingly) are present in the cortex in areas of brain damage and are enriched near A beta plaques. In postmortem human brain tissue, the expression level of this marker correlated with cognitive decline. Altogether, this study uncovers a shared signature of oligodendrocytes in central nervous system pathologies.

Automated summary

This study identifies a shared signature of oligodendrocytes in central nervous system pathologies. The researchers discovered a specific oligodendrocyte state, termed disease-associated oligodendrocytes (DOLs), that increased with brain pathology. DOLs were found in various neurodegenerative and inflammatory conditions, indicating a common response to severe pathological conditions.