Molecular pathogenesis and disease-modifying therapies of Alzheimer's disease and related disorders

• 資料種別: 記事
• タイトル: Molecular pathogenesis and disease-modifying therapies of Alzheimer's disease and related disorders
• 著者・編者: Takeshi Iwatsubo
• 出版事項: 日本 : Japan Medical Association
• 出版年月日等: 2022-07-15
• 出版年（W3CDTF）: 2022-07-15
• タイトル（掲載誌）: JMA Journal
• 巻号年月日等（掲載誌）: 5(3)
• 掲載巻: 5(3)
• ISSN（掲載誌）: 2433-3298
• ISSN-L（掲載誌）: 2433-328X
• 本文の言語コード: eng
• DOI: 10.31662/jmaj.2022-0079; https://doi.org/10.31662/jmaj.2022-0079
• 国立国会図書館永続的識別子: info:ndljp/pid/14494927; https://dl.ndl.go.jp/pid/14494927
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > 電子書籍・電子雑誌 > その他; https://dl.ndl.go.jp/collections/B00035
• 収集根拠: インターネット資料収集保存事業（WARP）
• 受理日（W3CDTF）: 2025-10-21T09:04:40+09:00
• 保存日（W3CDTF）: 2024-09-26
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: インターネット公開
• 遠隔複写可否（NDL）: 不可
• 掲載誌（URI）: https://warp.da.ndl.go.jp/info:ndljp/pid/13747952/www.jmaj.jp/detail.php?id=10.31662%2Fjmaj.2022-0079
• 掲載誌（国立国会図書館永続的識別子）: info:ndljp/pid/14494924; https://dl.ndl.go.jp/pid/14494924
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

• 要約等: <p>The deposition of amyloid β (Aβ) peptides as senile plaques and tau as neurofibrillary changes causes the hallmark neuropathological lesions of Alzheimer's disease (AD), which are implicated in its pathogenesis and deemed as the prime target for disease-modifying therapies (DMTs). Aβ is produced by sequential proteolytic cleavage by β- and γ-secretases. γ-Secretase, harboring presenilins (PS) as the catalytic center, forms the C-terminus of Aβ that determines its propensity to aggregate; missense mutations in PS genes cause familial AD by altering the preferred γ-secretase cleavage sites to increase the production of pathogenic Aβ42 species. Numerous DMTs for AD have been tested in clinical trials, some of which met the clinical endpoints, whereas others, especially those conducted in dementia stages, have failed, underscoring the needs for early intervention. Notably, positive outcomes of recent trials for anti-Aβ antibody drugs have depended largely on molecular imaging and fluid biomarkers, underscoring the needs of markers that surrogate the clinical and pathophysiological progression of AD. Longitudinal observational studies as represented by the AD Neuroimaging Initiative (ADNI) in North America, as well as the Japanese ADNI (J-ADNI), have contributed greatly toward the goal of very early treatment at the prodromal and preclinical AD stages by delineating the early natural course of AD and facilitating the development of biomarkers. It has been demonstrated that the clinical and biomarker profiles of prodromal AD in J-ADNI were remarkably similar to those in the North American ADNI, supporting the harmonization of global clinical trials. These clinical studies in Japan, accelerated by the development and implementation of biomarkers, will pave the way toward the development of AD therapies targeting its very early stages.</p>
• DOI: 10.31662/jmaj.2022-0079
• オンライン閲覧公開範囲: インターネット公開
• 連携機関・データベース: 科学技術振興機構 : J-STAGE; http://www.jstage.jst.go.jp

• 要約等: <p>The deposition of amyloid β (Aβ) peptides as senile plaques and tau as neurofibrillary changes causes the hallmark neuropathological lesions of Alzheimer's disease (AD), which are implicated in its pathogenesis and deemed as the prime target for disease-modifying therapies (DMTs). Aβ is produced by sequential proteolytic cleavage by β- and γ-secretases. γ-Secretase, harboring presenilins (PS) as the catalytic center, forms the C-terminus of Aβ that determines its propensity to aggregate; missense mutations in PS genes cause familial AD by altering the preferred γ-secretase cleavage sites to increase the production of pathogenic Aβ42 species. Numerous DMTs for AD have been tested in clinical trials, some of which met the clinical endpoints, whereas others, especially those conducted in dementia stages, have failed, underscoring the needs for early intervention. Notably, positive outcomes of recent trials for anti-Aβ antibody drugs have depended largely on molecular imaging and fluid biomarkers, underscoring the needs of markers that surrogate the clinical and pathophysiological progression of AD. Longitudinal observational studies as represented by the AD Neuroimaging Initiative (ADNI) in North America, as well as the Japanese ADNI (J-ADNI), have contributed greatly toward the goal of very early treatment at the prodromal and preclinical AD stages by delineating the early natural course of AD and facilitating the development of biomarkers. It has been demonstrated that the clinical and biomarker profiles of prodromal AD in J-ADNI were remarkably similar to those in the North American ADNI, supporting the harmonization of global clinical trials. These clinical studies in Japan, accelerated by the development and implementation of biomarkers, will pave the way toward the development of AD therapies targeting its very early stages.</p>
• DOI: 10.31662/jmaj.2022-0079; https://doi.org/10.31662/jmaj.2022-0079
• 関連情報（URI）: http://id.ndl.go.jp/digimeta/14494927; https://dl.ndl.go.jp/pid/14494927; https://www.jmaj.jp/download.php?id=10.31662/jmaj.2022-0079; https://search.jamas.or.jp/link/ui/2023252602
• 連携機関・データベース: 国立情報学研究所 : CiNii Research; https://cir.nii.ac.jp/
• 提供元機関・データベース: Japan Link Center; https://japanlinkcenter.org/top; 雑誌記事索引データベース; https://ndlsearch.ndl.go.jp; Crossref; https://www.crossref.org; 科学研究費助成事業データベース; https://kaken.nii.ac.jp/ja
• 書誌ID（NDLBibID）: 14494927; http://id.ndl.go.jp/bib/14494927