A study of predictors of Alzheimer's disease progression using data from large-scale longitudinal observational studies in Japan, the United States and Australia
| 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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Report
(4 results)
Research Products
(46 results)
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[Journal Article] A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer's disease.2020
Author(s)
Barthelemy NR, Goate AM, Morris JC, Ikeuchi T, Mori H, Shimada H, Shoji M, Suzuki K, Graff-Radford NR, Salloway S, Masters CL, O'Connor A, Fox NC, Levin J, Jucker M, Gabelle A, Lehmann S, Sato C, Bateman RJ, McDade E; Dominantly Inherited Alzheimer Network ,at al.
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Journal Title
Nat Med.
Volume: 26(3)
Issue: 3
Pages: 398-407
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Japanese and North American Alzheimer's Disease Neuroimaging Initiative studies: Harmonization for international trials.2018
Author(s)
Iwatsubo T, Iwata A, Suzuki K, Ihara R, Arai H, Ishii K, Senda M, Ito K, Ikeuchi T, Kuwano R, Matsuda H; Japanese Alzheimer's Disease Neuroimaging Initiative, Sun CK, Beckett LA, Petersen RC, Weiner MW, Aisen PS, Donohue MC; Alzheimer's Disease Neuroimaging Initiative
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Journal Title
Alzheimers Dement
Volume: S1552-5260
Issue: 8
Pages: 1-11
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] The Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Study in Japan: Report of Screening Data Results.2019
Author(s)
Takeshi Iwatsubo,Kazushi Suzuki,Ryoko Ihara,Chie Sakanaka,Yumi Umeda-Kameyama,Shinya Ishii,Kenji Kirihara,Atsushi Iwata,Chung-Kai Sun,Michael Donohue,Paul Aisen,Reisa Sperling
Organizer
12th Clinical Trials on Alzheimer's Disease (CTAD)
Related Report
Int'l Joint Research
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[Presentation] 被験者募集の電話対応に関する取り組みについて2019
Author(s)
徳山友希乃, 宮拝美恵, 宮本和子, 宮本和子, 柳田道孝, 坂中千恵, 鈴木一詩, 岩坪威, 井原涼子, 岩田淳, 森豊隆志
Organizer
第19回 CRCと臨床試験のあり方を考える会議
Related Report
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[Presentation] CSF and genetic biomarkers in MCI and AD subjects in J-ADNI for predicting future outcome.2017
Author(s)
Kazushi Suzuki, Ryoko Ihara, Atsushi Iwata, Takeshi Iwatsubo, Hiroyuki Arai, Kenji Ishii, Michio Senda, Kengo Ito, Takeshi Ikeuchi, Ryozo Kuwano, Hiroshi Matsuda, for the Japanese ADNI
Organizer
Clinical Trials on Alzheimer's Disease
Related Report
Int'l Joint Research
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[Presentation] Longitudinal cognitive and functional changes are influenced by educational history in the J-ADNI MCI individuals.2017
Author(s)
Atsushi Iwata, MD, Takeshi Iwatsubo, Kazushi Suzuki, Ryoko Ihara, Hiroyuki Arai, Kenji Ishii, Michio Senda, Kengo Ito, Takeshi Ikeuchi, Ryozo Kuwano, Hiroshi Matsuda, for the Japanese ADNI
Organizer
Clinical Trials on Alzheimer's Disease
Related Report
Int'l Joint Research
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[Presentation] Japanese ADNI: Clinical, neuroimaging and biomarker profiles in comparison with ADNI2017
Author(s)
Takeshi Iwatsubo, Atsushi Iwata, Kazushi Suzuki, Ryoko Ihara, Hiroyuki Arai, Kenji Ishii, Michio Senda, Kengo Ito, Takeshi Ikeuchi, Ryozo Kuwano, Hiroshi Matsuda, for the Japanese ADNI and Chung-Kai Sun, Laurel Beckett, Paul Aisen, Michael Donohue, for the ADNI
Organizer
Clinical Trials on Alzheimer's Disease
Related Report
Int'l Joint Research
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[Presentation] Clinical and psychometric characteristics of participants with preclinical Alzheimer’s disease in Japanese ADNI2017
Author(s)
Ryoko Ihara, Atsushi Iwata, Kazushi Suzuki, Takeshi Iwatsubo, Hiroyuki Arai, Kenji Ishii, Michio Senda, Kengo Ito, Takeshi Ikeuchi, Ryozo Kuwano, Hiroshi Matsuda, for the Japanese ADNI
Organizer
Clinical Trials on Alzheimer's Disease
Related Report
Int'l Joint Research
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