| Project/Area Number |
20K07783
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52010:General internal medicine-related
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| Research Institution | Tottori University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | アミロイド / 神経病理 / 免疫染色 / 認知症 / アルツハイマー / 脳脊髄液 |
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| Outline of Research at the Start |
アミロイド前駆体蛋白（APP）遺伝子新規変異（D678N）を我々は初めて見いだした．本研究計画では，本変異患者凍結脳から作成した本変異特異的抗アミロイド抗体を用いて，本遺伝子変異剖検脳ならびに孤発性アルツハイマー病ならびに老年性変化におけるアミロイド蓄積の病態を検証することを第一の目的とする．次に，本抗体を用いて，臨床的にアルツハイマー病が疑われる症例の脳脊髄液中の変異アミロイドの定量評価を行うことを第二の目的とする．
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| Outline of Final Research Achievements |
Specific antibodies against the mutant amyloid were generated from the brains of patients of the D67N family with a familial Alzheimer's disease mutation. Using this antibody, immunostaining was performed on the brains of patients with the mutation, sporadic Alzheimer's disease, and age-related senile plaques. The results showed that the mutation-specific antibody bound only to amyloid in the brains of patients with the mutation, but not to sporadic cases or senile plaques associated with aging. This indicates that the mechanism of amyloid accumulation differs between familial and sporadic Alzheimer's disease.
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| Academic Significance and Societal Importance of the Research Achievements |
本抗体が孤発性アルツハイマー病や加齢に伴うアミロイド沈着には結合せず，本変異特異的なアミロイド抗体であることが証明された．これにより，孤発例と家族性アルツハイマー病のアミロイド蓄積機序が異なることが示唆された．また，患者脳を検索する際に本抗体を用いることで本変異の有無を確認することができるようになった．
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