阿尔茨海默症(AD)是一种常见的神经退行性疾病。目前其发病机制尚不十分清楚，这使得我们难以找到干预AD的有效策略。Stern等人的研究为寻找干预AD的策略提供了新思路，他们在临床研究中发现了AD reserve现象，即机体可能存在某种机制有助于延缓AD疾病进程，这提示我们有可能通过加强相关机制干预AD。但是，reserve机制尚不十分清楚，阐明该机制是亟待解决的科学问题。为此我们提出科学假说：AD reserve机制之一可能与LMTK1磷酸化动态平衡对神经突触生长调控有关；LMTK1表达下降，减少磷酸化LMTK1的生成，抑制神经突触萎缩，从而延缓疾病进程。本项目从细胞和整体动物水平对所提出的科学假说进行验证，并建立基于机制的疾病进程模型探究LMTK1磷酸化动力学特征和抑制神经突触萎缩的新策略。本项目将为AD reserve现象提供一种新机制，有助于寻找干预AD的新靶点和新策略。

Alzheimer’s disease (AD) is a common neurodegenerative disease. As pathogenesis of AD is not yet fully elucidated, it is difficult to find strategies for AD intervention. Stern et al provide a new idea for investigating new strategies of AD intervention. In clinical researches, they found that AD progression could be delayed via certain mechanisms which is termed as reserve phenomenon. Therefore, it is possible to delay AD progression by enhancing the reserve mechanism. But the reserve mechanism remains unclear which is an issue needed to be addressed. In this project, a hypothesis is proposed for elucidating the reserve mechanism, that the reserve mechanism may be related to LMTK-1 phosphorylation dynamic balance which regulates the neurite growth. In the early stage of AD, the expression of LMTK-1 decreases which may reduce the LMTK-1 phosphorylation and inhibit neurite atrophy. In this project, the proposed hypothesis will be verified by in vitro and in vivo models. Furthermore, a mechanism based disease progression model will be developed to investigate the dynamics balance of LMTK-1 and the new strategy for preventing neurite atrophy. Our research will provide a new mechanism for AD reserve phenomenon which may contribute to finding new targets and strategies for AD intervention.