Multiscale network modeling of oligodendrocytes reveals molecular components of myelin dysregulation in Alzheimer's disease.

COLGS is highly enriched for genes encoding proteins identified in the myelin proteome [ 43 ] (Fold Enrichment (FE) = 1.92, Fisher’s Exact Test (FET) p = 2.4e-15), and is also enriched for genes specifically expressed in each of oligodendrocyte precursor cells (FE = 2.8, p = 4.2e-17), newly formed oligodendrocytes (FE = 6.2, p = 1.0e-84), and myelinating oligodendrocytes [ 32 ] (FE = 7.4, p = 2.5e-87), indicating that genes in COLGS capture a wide spectrum of OL functions. To systematically evaluate the AD genetics of COLGS, we identified 543 genes with nominally significant ( p < 0.05) gene-level associations with AD based on a meta-analysis of AD genome-wide association study (GWAS) data by the International Genomics of Alzheimer’s Project (IGAP) [ 28 ].

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The second human AD DEG signature is from a previous study that identified genes with a significant trend in RNA expression changes across the severity spectrum of AD (control, incipient, moderate, and severe) in the hippocampus (HIPP) [ 40 ].

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