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有晚发性阿尔茨海默病痴呆症遗传风险的年轻成年人的大脑功能异常。

Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia.

作者信息

Reiman Eric M, Chen Kewei, Alexander Gene E, Caselli Richard J, Bandy Daniel, Osborne David, Saunders Ann M, Hardy John

机构信息

Positron Emission Tomography Center, Banner Good Samaritan Medical Center, Phoenix, AZ 85006, USA.

出版信息

Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):284-9. doi: 10.1073/pnas.2635903100. Epub 2003 Dec 19.

Abstract

Fluorodeoxyglucose positron emission tomography (PET) studies have found that patients with Alzheimer's dementia (AD) have abnormally low rates of cerebral glucose metabolism in posterior cingulate, parietal, temporal, and prefrontal cortex. We previously found that cognitively normal, late-middle-aged carriers of the apolipoprotein E epsilon4 allele, a common susceptibility gene for late-onset Alzheimer's dementia, have abnormally low rates of glucose metabolism in the same brain regions as patients with probable AD. We now consider whether epsilon4 carriers have these regional brain abnormalities as relatively young adults. Apolipoprotein E genotypes were established in normal volunteers 20-39 years of age. Clinical ratings, neuropsychological tests, magnetic resonance imaging, and PET were performed in 12 epsilon4 heterozygotes, all with the epsilon3/epsilon4 genotype, and 15 noncarriers of the epsilon4 allele, 12 of whom were individually matched for sex, age, and educational level. An automated algorithm was used to generate an aggregate surface-projection map that compared regional PET measurements in the two groups. The young adult epsilon4 carriers and noncarriers did not differ significantly in their sex, age, educational level, clinical ratings, or neuropsychological test scores. Like previously studied patients with probable AD and late-middle-aged epsilon4 carriers, the young epsilon4 carriers had abnormally low rates of glucose metabolism bilaterally in the posterior cingulate, parietal, temporal, and prefrontal cortex. Carriers of a common Alzheimer's susceptibility gene have functional brain abnormalities in young adulthood, several decades before the possible onset of dementia.

摘要

氟脱氧葡萄糖正电子发射断层扫描(PET)研究发现,阿尔茨海默病性痴呆(AD)患者在扣带回后部、顶叶、颞叶和前额叶皮质的脑葡萄糖代谢率异常低。我们之前发现,载脂蛋白Eε4等位基因的认知正常的中老年携带者,这是晚发型阿尔茨海默病性痴呆的一个常见易感基因,在与可能患有AD的患者相同的脑区中葡萄糖代谢率异常低。我们现在考虑ε4携带者在相对年轻时是否就存在这些脑区异常。在20至39岁的正常志愿者中确定了载脂蛋白E基因型。对12名ε4杂合子(均为ε3/ε4基因型)和15名ε4等位基因非携带者进行了临床评分、神经心理学测试、磁共振成像和PET检查,其中12名非携带者在性别、年龄和教育水平上进行了个体匹配。使用一种自动算法生成了一个汇总的表面投影图,比较了两组的PET区域测量值。年轻的成年ε4携带者和非携带者在性别、年龄、教育水平、临床评分或神经心理学测试分数方面没有显著差异。与之前研究的可能患有AD的患者和中老年ε4携带者一样,年轻的ε4携带者在扣带回后部、顶叶、颞叶和前额叶皮质双侧的葡萄糖代谢率异常低。一种常见的阿尔茨海默病易感基因的携带者在成年早期就存在功能性脑异常,这比可能出现痴呆的时间早几十年。

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