Abstract
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(+) aOPCs in a serum-free defined medium; a subpopulation (~5%) of plexin-B3(+) aOPCs was also found. FGF2 withdrawal decreased NG2(+), but increased plexin-B3(+) aOPCs and Aβ1-42 secretion. Plexin-B3(+) aOPCs were distributed throughout the adult rat brain, although less densely than NG2(+) aOPCs. Spreading depolarization induced delayed cortical plexin-B3(+) aOPC gliosis in the ipsilateral remote cortex. Furthermore, extracellular Aβ1-42 accumulation was occasionally found around plexin-B3(+) 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(+) aOPCs may play essential roles in AD pathogenesis, as natural Aβ-secreting cells.