Cognitive deficits are ameliorated by reduction in amyloid β accumulation in Tg2576/p75^{NTR +/−} mice

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• 作者：Chongdong Jian^a ; ^b ; Donghua Zou^a ; Chun Luo^a ; Xixia Liu^a ; Lanqing Meng^b ; Jianmin Huang^b ; Xuebin Li^b ; Ruiya Huang^b ; Yuan Wu^a ; ^{wuyuan90@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Alzheimer's disease ; p75 neurotrophin receptor ; Aβ
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 June 2016
• 年：2016
• 卷：155
• 期：Complete
• 页码：167-173
• 全文大小：1065 K

文摘

Amyloid β (Aβ) is considered to be an important mediator of the development and progression of Alzheimer's disease (AD). Its direct binding to p75^NTR, not TrkA, induces apoptosis, which is thought to be the most relevant feature of p75^NTR regarding AD. In the present study we explored the regulation of p75^NTR on Aβ production and accumulation during AD pathology.

Materials and methods

We generated Tg2576/p75^NTR +/− mice by crossing the transgenic AD mice (Tg2576) with p75^NTR −/− mice to lower the p75^NTR level. Under these conditions, we evaluated cognitive function using the Morris water maze, pathology and process by which two types of Aβ (Aβ40 and Aβ42) are produced, by enzyme-linked immunosorbent assay and Western blotting.

Key finding

The results showed that cognitive deficits were rescued in Tg2576/p75^NTR +/− mice compared with those in Tg2576 mice. This cognitive functional recovery may be a consequence of a reduction in Aβ accumulation through the inhibition of β- and γ-secretase activities, without altering α-secretase activity.

Significance

Here, we investigated the mechanism by which p75^NTR regulates Aβ production and accumulation. Better understanding the relationship between p75^NTR and Aβ producing may help taking insight into the AD pathology.