In contrast, neuroinflammatory mediators and Alzheimer's disease (AD) biomarkers were largely unaffected.<h4>Conclusion</h4>Human AUD anterior frontal lobe WM pathology is accompanied by significant alterations in oligodendrocyte and astrocyte function, with alterations in Notch and insulin/IGF signaling. Here, INS is linked to early-onset autosomal dominant Alzheimer disease.