The role of oligodendrocyte lineage cells, the largest glial population in the adult central nervous system (CNS), in the pathogenesis of Alzheimer’s disease (AD) remains elusive. Here, we developed a culture method for adult oligodendrocyte progenitor cells (aOPCs). Fibroblast growth factor 2 (FGF2) promotes survival and proliferation of NG2
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aOPCs in a serum-free defined medium; a subpopulation (~5%) of plexin-B3
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aOPCs was also found. FGF2 withdrawal decreased NG2
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, but increased plexin-B3
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aOPCs and Aβ1-42 secretion. Plexin-B3
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aOPCs were distributed throughout the adult rat brain, although less densely than NG2
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aOPCs. Spreading depolarization induced delayed cortical plexin-B3
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aOPC gliosis in the ipsilateral remote cortex. Furthermore, extracellular Aβ1-42 accumulation was occasionally found around plexin-B3
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aOPCs near the lesions. In AD brains, virtually all cortical SPs were immunostained for plexin-B3, and plexin-B3 levels increased significantly in the Sarkosyl-soluble fractions. These findings suggest that plexin-B3
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aOPCs may play essential roles in AD pathogenesis, as natural Aβ-secreting cells.
In order to investigate the role of oligodendrocyte lineage cells in Alzheimer’s Disease (AD) pathology, Nihonmatsu-Kikuchi et al developed a culture method for adult oligodendrocyte progenitor cells in the rat. Using this method as well as imaging AD patient brain tissue, they found that plexin-B3-expressing cells could be a potential source of amyloid β peptide.