Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease
Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease
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DOI：
10.1073/pnas.0900345106
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发表时间：
2009-04-21
影响因子：
11.1
通讯作者：
Caselli, Richard J.
中科院分区：
文献类型：
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作者：
Reiman, Eric M.;Chen, Kewei;Caselli, Richard J.
在许多认知正常的老年人的大脑中发现了纤维状淀粉样蛋白（Aβ）。这是否反映了阿尔茨海默病（AD）的易感性尚不清楚。我们使用匹兹堡复合 B (PiB) PET 来表征认知正常老年人中 AD 遗传风险平均水平为 3 个的纤维状 A β 负荷与这种易感性之间的关系。使用动态 PiB PET 扫描、Logan 方法、统计参数映射和自动标记的感兴趣区域 (ROI) 来表征和比较 28 名认知正常的人（平均年龄 64 岁）的大脑与小脑 PIB 分布体积比（反映纤维 A β 负荷），这些人有 AD 家族史，载脂蛋白 E (APOE) epsilon 4 等位基因有 2 个拷贝、1 个拷贝和无拷贝。 8 个 epsilon 4 纯合子、8 个杂合子和 12 个非携带者在年龄、性别或认知评分方面没有显着差异。在受 AD 影响的平均皮质、额叶、颞叶、后扣带回楔前叶、顶叶和基底神经节 ROI 中，纤维 A beta 与 APOE epsilon 4 携带者状态和 epsilon 4 基因剂量显着相关，并且在最近出现轻度认知障碍的其他纯合子中最高。这些发现表明，认知正常的老年人中纤维状 A β 负荷与 APOE epsilon 4 基因剂量相关，APOE epsilon 4 基因剂量是 AD 的主要遗传风险因素。需要进行更多研究来追踪不同类型和不同程度的 AD 风险人群中纤维状 Aβ 的积累；确定纤维状 Aβ 单独或与其他生物标志物和风险因素组合预测认知能力下降和临床 AD 转化率的程度；并确定原纤维 Aβ 成像在一级预防试验中的作用。
Fibrillar amyloid-beta (A beta) is found in the brains of many cognitively normal older people. Whether or not this reflects a predisposition to Alzheimer's disease (AD) is unknown. We used Pittsburgh Compound B (PiB) PET to characterize the relationship between fibrillar A beta burden and this predisposition in cognitively normal older people at 3 mean levels of genetic risk for AD. Dynamic PiB PET scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest (ROIs) were used to characterize and compare cerebral-to-cerebellar PIB distribution volume ratios, reflecting fibrillar A beta burden, in 28 cognitively normal persons (mean age, 64 years) with a reported family history of AD and 2 copies, 1 copy, and no copies of the apolipoprotein E (APOE) epsilon 4 allele. The 8 epsilon 4 homozygotes, 8 heterozygotes, and 12 noncarriers did not differ significantly in terms of age, sex, or cognitive scores. Fibrillar A beta was significantly associated with APOE epsilon 4 carrier status and epsilon 4 gene dose in AD-affected mean cortical, frontal, temporal, posterior cingulate-precuneus, parietal, and basal ganglia ROIs, and was highest in an additional homozygote who had recently developed mild cognitive impairment. These findings suggest that fibrillar A beta burden in cognitively normal older people is associated with APOE epsilon 4 gene dose, the major genetic risk factor for AD. Additional studies are needed to track fibrillar A beta accumulation in persons with different kinds and levels of AD risk; to determine the extent to which fibrillar A beta, alone or in combination with other biomarkers and risk factors, predicts rates of cognitive decline and conversion to clinical AD; and to establish the role of fibrillar A beta imaging in primary prevention trials.