阿尔茨海默病小鼠模型中 Aβ 免疫与他汀类药物联合治疗。
Combined treatment of Aβ immunization with statin in a mouse model of Alzheimer's disease.
机构信息
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656, USA.
出版信息
J Neuroimmunol. 2012 Mar;244(1-2):70-83. doi: 10.1016/j.jneuroim.2012.01.008. Epub 2012 Feb 11.
Abstract
We evaluated the therapeutic efficacy of combined treatment of Aβ-immunization with simvastatin in an Alzheimer mouse model at age 22 months. DNA prime-adenovirus boost immunization induced modest anti-Aβ titers and simvastatin increased the seropositive rate. Aβ-KLH was additionally administered to boost the titers. Irrespective of simvastatin, the immunization did not decrease cerebral Aβ deposits but increased soluble Aβ and tended to exacerbate amyloid angiopathy in the hippocampus. The immunization increased cerebral invasion of leukocytes and simvastatin counteracted the increase. Thus, modest anti-Aβ titers can increase soluble Aβ and simvastatin may reduce inflammation associated with vaccination in aged Alzheimer mouse models.
摘要
我们评估了 Aβ 免疫接种与辛伐他汀联合治疗在 22 月龄阿尔茨海默病小鼠模型中的疗效。DNA 疫苗初免-腺病毒加强免疫诱导了适度的抗 Aβ 滴度，辛伐他汀增加了血清阳性率。另外给予 Aβ-KLH 以提高滴度。无论是否使用辛伐他汀，免疫接种都不能减少脑内 Aβ 沉积，但增加了可溶性 Aβ，并倾向于加重海马的淀粉样血管病。免疫接种增加了脑内白细胞浸润，而辛伐他汀则对抗这种增加。因此，适度的抗 Aβ 滴度可能会增加可溶性 Aβ，而辛伐他汀可能会减少与老年阿尔茨海默病小鼠模型疫苗接种相关的炎症。
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2
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