雑誌文献を検索します。書籍を検索する際には「書籍検索」を選択してください。

検索

書誌情報 詳細検索 by 医中誌

Japanese

Molecular Genetics and Protein Molecules in Dementia Maria KANO 1 , Taisuke TOMITA 1 1Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo Keyword: アミロイドβ , タウ , アルツハイマー病 , 17番染色体に連鎖する家族性前頭側頭型認知症パーキンソニズム , 家族性変異 , amyloid β , tau , Alzheimer disease , FTLD-17 , familial mutations pp.873-882
Published Date 2025/9/10
DOI https://doi.org/10.11477/mf.030126030530050873
  • Abstract
  • Look Inside
  • Reference

 Alzheimer's disease (AD), the most common cause of dementia, is marked by the pathological accumulation of misfolded proteins in the brain. Its key pathological features include extracellular amyloid β (Aβ) plaques and intracellular tau neurofibrillary tangles, both of which contribute to synaptic dysfunction and neuronal death. Familial AD is linked to mutations in the APP, PSEN1, or PSEN2 genes, which promote increased Aβ production or aggregation. In contrast, frontotemporal dementia (FTD), including FTDP-17, is associated with MAPT mutations that lead to tau fibril accumulation independent of Aβ pathology. Recent advances in cryo-electron microscopy (cryo-EM) have revealed disease-specific conformations of Aβ and tau fibrils at atomic resolution, highlighting the role of structural polymorphism in disease progression. Aβ contributes to synaptic deficits and activates glial cells, thereby initiating neuroinflammatory responses. Genetic risk factors such as APOE and TREM2 influence these pathological processes. Transgenic mouse models carrying familial mutations have replicated certain aspects of AD pathology. However, most models fail to fully reproduce the human-like filament structures or the sequential progression from Aβ to tau pathology. Novel knock-in models, combined with cryo-EM-based validation, now provide a more accurate platform for studying disease mechanisms and developing targeted therapies.


Copyright © 2025, Igaku-Shoin Ltd. All rights reserved.

基本情報

電子版ISSN 1882-1251 印刷版ISSN 0301-2603 医学書院

関連文献

もっと見る

文献を共有