Research for the pathological relationship between Alzheimer Disease and depression

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K15438
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: TATEBAYASHI Yoshitaka 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, プロジェクトリーダー (80342814)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: オリゴデンドロサイト前駆細胞 / アルツハイマー病 / 大うつ病 / plexin-B3 / 老人斑 / アミロイドβ

Outline of Final Research Achievements

The roles of oligodendrocyte (OL) lineage cells, the largest glial population in the adult CNS, in the pathogenesis of Alzheimer’s disease (AD) remain elusive. Here, we show a newly developed culture method for adult OL progenitor cells (aOPCs) and identify novel plexin-B3-expressing aOPCs as β amyloid peptides (Aβ)-secreting cells. A small population of plexin-B3+ aOPCs was found in NG2+ aOPC cultures (> 95%) growing in FGF2. FGF2 withdrawal decreased NG2+, but increased plexin-B3+ aOPCs with increased Aβ1-40, -42 secretions and Aβ1-42/total Aβ ratios. In vivo, plexin-B3+ aOPCs are distributed throughout the adult brain, although less densely so than NG2+ aOPCs. Spreading depolarization, a type of brain injury, induced unique delayed cortical plexin-B3+ aOPC gliosis. In AD brains, virtually all senile plaques were immunostained with plexin-B3 antibodies. These findings suggest that plexin-B3+ aOPCs play important roles in AD pathogenesis as a natural Aβ source.

Free Research Field

精神医学