Aβ过度生成是阿尔茨海默病（AD）发生的关键机制，导致β淀粉样斑块形成和认知障碍。内质网应激激活的未折叠蛋白反应（UPR）促进Aβ生成。我们研究显示apelin/APJ系统抑制UPR，但apelin/APJ对Aβ生成的作用还不清楚。Aβ前体蛋白经BACE1和γ-分泌酶剪切生成Aβ，TMP21是γ-分泌酶的调节因子。UPR上调BACE1表达，而BACE1升高和TMP21降低促进Aβ生成。我们预实验显示apelin/APJ在AD中显著下调,而apelin/APJ干预可缓解UPR及BACE1和TMP21的异常调控，降低Aβ生成。据此提出科学假设：apelin/APJ通过缓解UPR介导的BACE1和TMP21异常调控而抑制Aβ生成。我们将以apein/APJ对Aβ生成的作用为切入点，明确apein/APJ对Aβ生成的调控作用和机制及对β淀粉样斑块形成和认知障碍的影响，为AD治疗提供新策略。

Increased Aβ generation is the major cause of the pathogenesis of Alzheimer’s disease(AD), resulting in amyloid plaque formation and cognitive deficits. Endoplasmic reticulum stress（ERS）-activated unfolded protein response (UPR)promotes Aβ generation. Our previous studies showed that apelin/APJ attenuates UPR. However, the role of apelin/APJ in Aβ generation remains elusive. Aβ is generated from Aβ precursor protein by sequential cleavages of BACE1 and γ-secretase, while TMP21 is a regulator of γ-secretase. UPR increases BACE1 expression, while increased BACE1 and reduced TMP21 promote Aβ generation. Our preliminary data showed that apelin/APJ attenuates UPR and the dysregulation of BACE1 and TMP21 in AD, and reduces Aβ generation. Thus, we proposed that apelin/APJ inhibits Aβ generation by attenuating UPR-mediated dysregulation of BACE1 and TMP21. We plan to further determine the role of apelin/APJ in Aβ generation, amyloid plaque formation and cognitive deficits in AD, and elucidate the underlying mechanisms. This study will provide a novel strategy for AD treatment.