The characterization of regulatory T cells in neuroinflammation of Alzheimer's disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22789
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Keio University
• Principal Investigator: OHYAGI Masaki 慶應義塾大学, 医学部(信濃町), 特任助教 (70882497)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 認知症 / アルツハイマー病 / 脳内炎症

Outline of Final Research Achievements

App knock-in mouse, a mouse model of cerebral amyloidosis, increased cerebral amyloid β plaque deposition and enhanced neuroinflammation, including activation of microglia and astrocyte, with aging. Regulatory T cells (Treg) infiltration into the brain also increased. Foxp3+Treg depletion increased cerebral amyloid β plaque deposition. Single-cell RNA-seq analysis revealed that Treg infiltrating into App knock-in mouse brain upregulated several genes associated with the regulation of immune responses. These findings suggest a key role of brain-infiltrating Treg in β-amyloid pathology.

Free Research Field

神経免疫

Academic Significance and Societal Importance of the Research Achievements

高齢化に伴い我が国の認知症患者数は急増しており、特にアルツハイマー病は認知症患者の半数以上を占めるが、未だ根治治療法はなく現行治療は症状軽減にとどまっている。アルツハイマー病患者脳では異常タンパク凝集と脳内炎症が亢進しており、本研究結果から生体に本来備わっている免疫調節機構の中心である制御性T細胞がアルツハイマー病の病態に深く関与していることが示唆され、今後の治療戦略につながることが期待される。