Fig. 4: Oligodendrocyte response in AD.

a, Oligodendrocytes provide metabolic and trophic support to neurons. Myelin damage not only disrupts oligodendroglial support mechanisms, but dysfunctional myelin itself induces axonal damage and is detrimental for axonal survival. b, Myelin dysfunction drives amyloid plaque deposition in AD. Mechanistically, myelin dysfunction leads to accumulation of Aβ-producing machinery in axonal swellings, leading to higher Aβ production. Additionally, myelin damage engages disease-associated microglia, interfering with their ability to clear amyloid plaques. IFN, interferon; MHC-II, major histocompatibility complex class II. c, Myelin damage in AD is marked by increased CD8⁺ T cell infiltration in the brain. Mechanistically, CD8⁺ T cells abnormally activate microglia to damage myelin, driving a self-propelling loop, in which enhanced myelin damage drives further neuroinflammation. d, Oligodendrocytes show enrichment in genes associated with the amyloid-processing pathway (such as APP, BACE1, PSEN1 and PSEN2), thereby contributing to the total Aβ plaque load. Figure created using BioRender.com.