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Establishing a diagnostic method for the preclinical stage of sporadic late-onset Alzheimer's disease based on retinal layer thickness and genetic and environmental factors

Research Project

Project/Area Number 21K10440
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 58030:Hygiene and public health-related: excluding laboratory approach
Research InstitutionTohoku University

Principal Investigator

Taira Makiko  東北大学, 東北メディカル・メガバンク機構, 助教 (60792140)

Co-Investigator(Kenkyū-buntansha) 布施 昇男  東北大学, 東北メディカル・メガバンク機構, 教授 (10302134)
川崎 良  大阪大学, 大学院医学系研究科, 教授 (70301067)
三木 篤也  愛知医科大学, 医学部, 教授 (30437404)
小島 要  東北大学, 東北メディカル・メガバンク機構, 講師 (10646988)
田高 周  東北大学, 東北メディカル・メガバンク機構, 講師 (60815463)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2023: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords晩期発症型アルツハイマー型認知症 / 網膜層厚測定 / ApoE / 光干渉断層計 / 網膜断層画像撮像 / 網膜層厚変化 / 遺伝因子 / 環境因子 / アルツハイマー病前臨床期 / 光干渉断層計(OCT) / 遺伝環境因子 / Klotho遺伝子
Outline of Research at the Start

本研究では、認知症の約半数を占める孤発性の晩期(65歳以降)発症型アルツハイマー病について、血液による遺伝子解析、問診からの生活習慣・環境に関する個別の背景情報、迅速で非侵襲的な眼科検査による網膜層厚測定結果から早期の発症予測が可能な診断指標の確立を行う。本研究で確立した診断指標により、高価で時間を要したMRIや更に薬剤静注を求めたPETの代替として、多くの晩期発症型アルツハイマー病前臨床期高齢者の健康状態の把握が簡便に可能となり、個人の病態進行に照準をあわせた予防医療の実現が期待される。

Outline of Final Research Achievements

This research aims to establish diagnostic indicators capable of early onset prediction from retinal layer thickness, considering the mechanisms of changes in retinal thickness induced by genetic and environmental factors during the preclinical phase of late-onset Alzheimer’s disease (LOAD). LOAD currently accounts for approximately half of all dementia patients. The diagnostic indicators established in this study, which are anticipated to serve as alternatives to costly and time-consuming MRI and PET imaging, could greatly simplify the assessment of the health status of many elderly individuals in the preclinical phase of LOAD. The urgent societal demand for preventive healthcare tailored to individual disease progression has grown significantly in recent years, underscoring the necessity of this research.

Academic Significance and Societal Importance of the Research Achievements

学術的意義として、1. 網膜においてのLOAD前臨床期に網膜神経節細胞消失を伴う網膜神経線維層(RNFL)の菲薄化、 2. LOADの予後規定因子の一つとしての、ApoE遺伝子ε4の保有とKlotho遺伝子ヘテロ接合性変異の保有 を挙げた。 特に2に関する既報の検討はほぼ全て非日本人における成果と考えられており、社会的意義としても、日本人集団での検討は前例をみないと考えている。本研究の成果をもとに、異動先(順天堂大学医学部神経学講座)において、引き続き研究成果を論文作成に換える予定である。

Report

(2 results)
  • 2024 Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (5 results)

All 2023 2022 Other

All Int'l Joint Research (1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] Indiana University(米国)

    • Related Report
      2022 Research-status Report
  • [Presentation] GENOME-WIDE ASSOCIATION STUDY (GWAS) BY PROXY OF ALZHEIMER'S DISEASE RISK IN A VERY LARGE (N=95,000) JAPANESE OBSERVATIONAL COHORT STUDY2023

    • Author(s)
      Makiko Taira
    • Organizer
      17th International Conference on Alzheimer’s and Parkinson’s Diseases: Mechanisms, Clinical Strategies and promising Treatments of Neurodegenerative Diseases
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Genome-wide association study of brain MRI and other phenotypes in the Tohoku Medical Megabank Organization2023

    • Author(s)
      Makiko Taira
    • Organizer
      AAIC 2023
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] GENOME-WIDE ASSOCIATION STUDY BY PROXY (GWAX) OF ALZHEIMER'S DISEASE RISK IN A VERY LARGE JAPANESE OBSERVATIONAL COHORT STUDY2023

    • Author(s)
      Makiko Taira
    • Organizer
      第64回日本神経学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 住民コホート調査の認知症ゲノム解析2022

    • Author(s)
      平良 摩紀子
    • Organizer
      第24回東北老年期認知症研究会
    • Related Report
      2022 Research-status Report

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Published: 2021-04-28   Modified: 2026-01-16  

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