| Project/Area Number |
17K09794
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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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| Research Field |
Neurology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Suzuki Kazushi 東京大学, 医学部附属病院, 特任助教 (30529053)
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| Co-Investigator(Kenkyū-buntansha) |
岩田 淳 東京大学, 医学部附属病院, 准教授 (40401038)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | アルツハイマー病 / 軽度認知障害 / アミロイドβ / APOE / タウ / リン酸化タウ / プレクリニカルAD / J-ADNI / アミロイドPET / カルシウム / ADNI / バイオマーカー / 脳神経疾患 / preclinical AD |
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| Outline of Final Research Achievements |
We reported that the positive rate of amyloid accumulation in mild cognitive impairment (MCI) and the rate of post-onset progression in Japan were similar to those in the United States. Amyloid accumulation was also observed in about one in four (22.4%) of cognitively normal Japanese elderly patients. These reports are the first in Japan based on a nationwide study. Novel predictors of worsening MCI and early Alzheimer's disease were also reported, such as chronic kidney disease in stage G2 or higher, low serum calcium levels, high levels of total tau and phosphorylated tau in cerebrospinal fluid, poor cognitive performance on memory tasks, and atrophy of the temporal lobe region on MRI. Some of these factors are of particular importance in terms of developing novel therapies. We further showed that the retention of the APOE gene ε4 allele, a major genetic risk factor for the development of AD, had no effect on the rate of deterioration two years after the onset of early AD.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果からプレクリニカルAD期からMCI、軽度AD期までの日本人における自然歴が初めて数値として明確に示され、臨床研究や治験結果の定量的な検証や日米間の比較検討が可能となった。また報告した予後悪化因子の中でも、特に慢性腎臓病、血清カルシウム低値等は内科的な治療介入が奏効する可能性をも示唆するものでもあり、追随研究による検証が俟たれる。さらに近年のAD治療薬治験では、治療/対照群間のε4アレル頻度の差が治療効果に与えた影響がしばしば議論となるが、本研究の報告はその影響は無視できるほど小さいことを直接的に示したものであり、社会的意義が大きい。
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