Monoclonal anti-proprotein convertase subtilisin/kexin type 9 (PSCK9) neutralizing antibodies effectively lower plasma cholesterol levels and decrease cardiovascular events but also raised some concern that cognitive function could worsen as a side effect. Here, we performed experiments in mice to characterize the effect of anti-PCSK9 antibodies on behavior and cognitive function in detail.

APOE*3Leiden.CETP mice and B6129SF1/J wildtype mice were fed a Western type diet and treated with the fully human anti-PCSK9 antibody CmAb1 (PL-45134; 10mg*kg^-1 s.c.) or vehicle for 6 weeks. Locomotor activity, anxiety levels, recognition memory, and spatial learning were investigated using the open field, novel object recognition test, and Morris water maze, respectively.

Serum cholesterol levels in APOE*3Leiden.CETP mice after treatment with anti-PCSK9 antibody were significantly lower compared to controls whereas cholesterol levels in B6129SF1/J wildtype mice remained unchanged at low levels. No apparent differences were found regarding locomotor activity, anxiety, recognition memory, and spatial learning between animals treated with anti-PCSK9 antibody or vehicle in APOE*3Leiden.CETP and B6129SF1/J wildtype mice.

In this study, we found no evidence that treatment with anti-PCSK9 antibodies lead to differences in behavior or changes of cognition in mice.

单克隆抗前蛋白转化酶枯草杆菌蛋白酶 / kexin 9 型 (PSCK9) 中和抗体可有效降低血浆胆固醇水平并减少心血管事件，但也引起了一些担忧，即认知功能可能会因副作用而恶化。在这里，我们在小鼠中进行了实验，以详细描述抗 PCSK9 抗体对行为和认知功能的影响。

APOE*3Leiden.CETP 小鼠和 B6129SF1/J 野生型小鼠被喂食西式饮食，并用全人抗 PCSK9 抗体 CmAb1（PL-45134；10mg*kg ^-1 sc）或载体治疗 6 周。分别使用开放场、新物体识别测试和莫里斯水迷宫调查运动活动、焦虑水平、识别记忆和空间学习。

与对照相比，APOE*3Leiden.CETP 小鼠在用抗 PCSK9 抗体处理后的血清胆固醇水平显着降低，而 B6129SF1/J 野生型小鼠的胆固醇水平保持在低水平不变。在 APOE*3Leiden.CETP 和 B6129SF1/J 野生型小鼠中，用抗 PCSK9 抗体或载体治疗的动物在运动活动、焦虑、识别记忆和空间学习方面没有发现明显差异。

在这项研究中，我们没有发现任何证据表明用抗 PCSK9 抗体治疗会导致小鼠行为差异或认知变化。