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Alzheimer's Disease, Other Dementia, Aging

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

An endogenous peptide to recover amyloid β oligomer-induced cognitive dysfunction

  • P2-293
  • 宮野 貴士 / Takashi Miyano:1 佐藤 翔太 / Shota Sato:1 真鍋 裕子 / Yuko Manabe:1 吉田 渚 / Nagisa Yoshida:1 木村 彩乃 / Ayano Kimura:2 羽田 沙緒里 / Saori Hata:2 鈴木 利治 / Toshiharu Suzuki:2 井上 剛 / Tsuyoshi Inoue:1 
  • 1:岡山大院・医歯薬・生体分子解析学 / Dept of Biophys Chem, Grad Sch of Med Dent and Pharm Sci, Okayama Univ 2:北大院・薬・神経科学 / Dept of Neurosci, Grad Sch of Pharm Sci, Hokkaido Univ 

Alzheimer's disease is a major neurodegenerative disease with memory impairment. Amyloid precursor protein is sequentially cleaved by β/γ-secretases, and finally releases the amyloid β (Aβ) peptide. Low aggregated form of Aβ (Aβ oligomer) is proposed as a trigger of Alzheimer's disease. Actually, previous studies showed that acute intracerebroventricular (i.c.v.) injection of Aβ oligomer in mice leads to memory impairment, and also weakens θ oscillations in the hippocampus (5~8 Hz) related to learning and memory. In this study, we explored an endogenous peptide to recover the Aβ oligomer-induced dysfunction in vivo. To address this issue, we focused on p3-Alcβ peptide which is released from Alcadeinβ expressed specifically in neurons, because this peptide is also produced by γ-secretase cleavage in the same manner as Aβ. First, we assessed effects of p3-Alcβ on the cognitive dysfunction using novel object recognition test. An i.c.v. injection of Aβ oligomer (1 μM) impaired the memory performance. However, co-injection of p3-Alcβ (10 μM) fully recovered the Aβ oligomer-induced memory impairment. Second, we assessed the neural dysfunction by recording the θ oscillations in the hippocampus of awake mice. An i.c.v. injection of Aβ oligomer (1 μM) decreased the power of θ oscillation. However, co-injection of p3-Alcβ (10 μM) improved the Aβ oligomer-induced attenuation of θ oscillations. We further found that p3-Alcα, another p3-Alc peptide released from Alcadeinα, has no effects on the Aβ oligomer-induced cognitive and neural dysfunction. These results show that endogenous peptide p3-Alcβ improves Aβ oligomer-mediated cognitive and neural dysfunction in mice. We propose that p3-Alcβ is a new therapeutic target for Alzheimer's disease.

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