Using Oligodendrocytes for studies in Alzheimer disease

Genomic regulatory architecture (GRA) has been primarily studied in European ancestry. As part of the functional Consortium of the Alzheimer Disease Sequencing Project, we are determining the GRA in African and Amerindian ancestries. Oligodendrocytes (OLs) are the largest glial population in the adult central nervous system. While their main role is to support neuronal metabolism and connectivity, few studies have examined their importance in Alzheimer’s disease (AD), despite reports of low numbers of oligodendrocytes and reduced myelin in the early stages of AD and a demonstrated role of myelinating oligodendrocytes in learning and memory. Several studies have reported the derivation of OLs from pluripotent cells, such as induced pluripotent stem cells (iPSC) to be challenging. Here, we optimized a protocol to derive oligodendrocytes from iPSC for studies in AD patients with different ancestries and how ancestry‐specific genomic differences drive the onset and pathogenesis of AD.