2019 Fiscal Year Final Research Report

In vivo imaging for pathological substance and neuroinflammation/neuroactivity and therapeutic strategy in Alzheimer's disease

Research Project

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Project/Area Number	17H04247
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Psychiatric science
Research Institution	Hamamatsu University School of Medicine
Principal Investigator	Ouchi Yasuomi 浜松医科大学, 光尖端医学教育研究センター, 教授 (40436978)
Co-Investigator(Kenkyū-buntansha)	横倉正倫浜松医科大学, 医学部, 助教 (00529399) 武内智康浜松医科大学, 光尖端医学教育研究センター, 特任助教 (20754188) 和久田智靖浜松医科大学, 医学部附属病院, 講師 (80444355)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	アルツハイマー病 / 脳神経画像
Outline of Final Research Achievements	We tried to develop an imaging method using a molecular probe which produced an MRI signal for FKN and a radioisotope (RI) probe for CB2, in order to establish a new in vivo imaging technique to visualize pathological substances and M2-type neuroinflammation along with neuronal survival and synapse density in the living brain of Alzheimer’s disease (AD). The MRI signal was found to be too small possibly because the degree of the probe entering into the cell was insufficient, which might require much higher magnetic field MRI machine. In contrast, the RI probe successfully allowed imaging of M2-type cell by targeting CB2 receptor in vivo. The activation of M2 like neuroinflammation was shown to precede M1 activation at an early stage of AD model (senescence-accelerated mouse prone 10, the line of mice generating amyloid and neuronal loss). The result provided a therapeutic contention that persisting M2 activity might be a beneficial in tempering the progression of AD
Free Research Field	脳神経画像学
Academic Significance and Societal Importance of the Research Achievements	アルツハイマー病（AD）の脳内でミクログリア活性が上昇し、その活性の強さはアミロイド蛋白（Aβ）の蓄積程度と逆相関があることを報告した。弧発性ADモデルマウス（SAMP8）でAβ出現前に神経新生が促進され、ミクログリア活性の保護性刺激が神経新生を促すことが報告された。そのためAD発症後のAβ標的療法だけでなく、ADの予防や進行抑制にAβ発現に伴う神経新生の促進と活性化ミクログリアへの介入が重要であると考えられた。本研究では、ADモデルマウスでM2系ミクログリア活性の活性化とAβの関与がわかり、AD治療ターゲットを異常蛋白以外にも視点を向ける重要性が示唆された。