This model is supported by the results presented here demonstrating that although diabetes-associated sulfatide deficiency initiates in the periphery, it can eventually progress to the brain at advanced disease stages, at which point it could contribute to AD pathogenesis by accelerating brain sulfatide deficiency, a process that in the context of AD is mediated by apolipoprotein E and accelerated by amyloid-β (72). Here, APOE is linked to Alzheimer disease.