PNAS:糖尿病和阿尔茨海默氏症并发会加剧危害

2010-04-07 00:00 · Bob

日本研究人员近日发现,如果患者同时患有糖尿病和阿尔茨海默氏症(Alzheimer disease),两种疾病将相互产生不良影响。这一研究成果已刊登在最新一期《美国科学院学报》(PNAS)网络版上。 大阪大学教授森下龙一和副教授里直行率领的研究小组将患有糖尿病的老鼠与患有阿尔茨海默

日本研究人员近日发现,如果患者同时患有糖尿病和阿尔茨海默氏症(Alzheimer disease),两种疾病将相互产生不良影响。这一研究成果已刊登在最新一期《美国科学院学报》(PNAS)网络版上。

大阪大学教授森下龙一和副教授里直行率领的研究小组将患有糖尿病的老鼠与患有阿尔茨海默氏症的老鼠交配,培育出同时患有两种疾病的老鼠。

在记忆力实验中,一般的阿尔茨海默氏症老鼠出现记忆障碍是在出生至3至6个月的时候,而合并症老鼠在出生后约2个月就出现了症状,发病时间大为提前。

在糖耐量测试中,同时患有两种疾病的老鼠的血糖值更容易升高。

里直行说,类似现象也会出现在人的身上。尽早戒除不良生活习惯可以降低人们罹患这两种疾病的风险。

更多阅读

  PNAS发表论文摘要(英文)

Published online before print March 15, 2010, doi: 10.1073/pnas.1000645107

Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Aβ deposition in an Alzheimer mouse model with diabetes

Shuko Takedaa,b, Naoyuki Satoa,b, Kozue Uchio-Yamadac, Kyoko Sawadac, Takanori Kuniedac, Daisuke Takeuchia,b, Hitomi Kurinamia,b, Mitsuru Shinoharaa,b, Hiromi Rakugib, and Ryuichi Morishitaa,1

Abstract

Recent epidemiological studies suggest that diabetes mellitus is a strong risk factor for Alzheimer disease. However, the underlying mechanisms remain largely unknown. In this study, to investigate the pathophysiological interaction between these diseases, we generated animal models that reflect the pathologic conditions of both diseases. We crossed Alzheimer transgenic mice (APP23) with two types of diabetic mice (ob/ob and NSY mice), and analyzed their metabolic and brain pathology. The onset of diabetes exacerbated Alzheimer-like cognitive dysfunction without an increase in brain amyloid-β burden in double-mutant (APP+-ob/ob) mice. Notably, APP+-ob/ob mice showed cerebrovascular inflammation and severe amyloid angiopathy. Conversely, the cross-bred mice showed an accelerated diabetic phenotype compared with ob/ob mice, suggesting that Alzheimer amyloid pathology could aggravate diabetes. Similarly, APP+-NSY fusion mice showed more severe glucose intolerance compared with diabetic NSY mice. Furthermore, high-fat diet feeding induced severe memory deficits in APP+-NSY mice without an increase in brain amyloid-β load. Here, we created Alzheimer mouse models with early onset of cognitive dysfunction. Cerebrovascular changes and alteration in brain insulin signaling might play a pivotal role in this relationship. These findings could provide insights into this intensely debated association.

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