＜Symposium IV＞Oligomeric Aβ is the sole culprit molecule to cause Alzheimer's disease?
- フォーマット:
- 論文
- 責任表示:
- Mori, Hiroshi ; Tomiyama, Takami ; Ishibashi, Kennichi ; Ohnishi, Kiyouhisa ; Teraoka, Rie ; Fukushima, Akiko ; Takuma, Hiroshi ; Shimada, Hiroyuki ; Ataka, Suzuka ; Umeda, Tomohiro ; Kitajima, Erika ; Fujita, Yuki ; Yamashita, Yuki ; Yamamoto, Keiichi ; Miki, Takami ; Matsuyama, Shogo ; Iso, Hiroyuki ; Nagata, Tetsu ; Nishizaki, Tomoyuki ; Wada, Yasuhiro ; Yoshioka, Eito ; Watanabe, Yasuyoshi
- 言語:
- 英語
- 出版情報:
- 弘前大学大学院医学研究科・弘前医学会, 2010-07-08
- 著者名:
- 掲載情報:
- 弘前医学
- ISSN:
- 0439-1721
- 巻:
- 61
- 通号:
- Supplement
- 開始ページ:
- S105
- 終了ページ:
- S110
- バージョン:
- publisher
- 概要:
- Alzheimer's disease (AD) is the major and common disease usually for aged people to show progressive neurodegenerative disorder with the dementia. Amyloid-beta （also β-protein and referred here to as Aβ） is a wellestablished … seminal peptide in AD that is produced from the amyloid precursor protein （APP） by consecutive digestions with β-secretase of BACE and gamma-secretase of the presenilin complex. Abnormal cerebral accumulation of Aβ such as insoluble fi brils in senile plaques and cerebral amyloid angiopathy （CAA） are observed as a neuropathological hallmark of AD. In contrast to such insoluble fi brillary Aβ, a soluble oligomeric complex is discussed as ADDLs, Aβ oligomer, low-n oligomer Aβ, Aβ*56 or so. Despite their diff erent names, it is proposed as the current hypothesis that oligomeric Aβ is the direct molecule to cause synaptic toxicity and cognitive dysfunction in the early stages of AD. We identifi ed a novel APP mutation （E693delta; referred to as the Osaka mutation） in a pedigree with probable AD resulting in a variant Aβ lacking glutamate at position 22. Based on theoretical prediction and in vitro studies on synthetic mutant Aβ peptides, the mutated Aβ peptide showed a unique aggregation property of enhanced oligomerization but no fi brillization. This was further confi rmed by PiB-PET analysis on the proband patient. Collectively together, we conclude that the Osaka mutation is the fi rst human evidence for the hypothesis that oligomeric Aβ is involved in AD. 続きを見る
- URL:
- http://hdl.handle.net/10129/3676
類似資料:
|
弘前大学大学院医学研究科・弘前医学会 | |
|
11
論文
Phenotypic Characterization of Early Biliary Tract Carcinomas Proposes Two Carcinogenesis Pathways
弘前大学大学院医学研究科・弘前医学会 | |
