Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers
Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers
复制标题
DOI：
10.1212/wnl.0b013e31825fdf18
复制
发表时间：
2012-07-01
期刊：
影响因子：
9.9
通讯作者：
Nordberg, Agneta
中科院分区：
文献类型：
--
作者：
Scholl, Michael;Wall, Anders;Nordberg, Agneta
目的：首次通过 PET 体内研究北极 APP (APParc) 早发家族性阿尔茨海默病 (eoFAD) 突变的特殊病理学，并与其他 eoFAD 突变和散发性阿尔茨海默病 (sAD) 进行比较。方法：我们使用 C-11 标记的匹兹堡化合物 B (PiB) 和 F-18-氟脱氧葡萄糖对 2 名 APParc 突变携带者以及 5 名非携带者兄弟姐妹进行横断面检查(FDG) PET，以及 MRI、CSF 生物标志物和神经心理学测试。同样，我们检查了 7 名 sAD 患者、1 名早老素 1 (PSEN1) 突变携带者、1 名瑞典 APP (APPswe) 突变携带者和 7 名健康对照 (HC)。结果：APParc 突变携带者的皮质 PiB 保留非常低，而脑葡萄糖代谢和 CSF 的 A beta(1-42)、总和磷酸化 tau 水平明显病理性。这与 PSEN1 和 APPswe 突变携带者形成鲜明对比，PSEN1 和 APPswe 突变携带者显示出皮层和纹状体中高 PiB 保留，并伴有异常的葡萄糖代谢和脑脊液生物标志物，而 sAD 患者与 HC 相比，通常表现出高皮质 PiB 保留和病理性 CSF 水平以及葡萄糖代谢降低。葡萄糖代谢和 CSF 中 A beta (1-42) 水平降低，其他形式的 A beta（例如寡聚物和原纤维）对于导致临床阿尔茨海默病的病理过程很重要。神经病学(R)2012;79:229-236
Objective: To investigate the particular pathology of the Arctic APP (APParc) early-onset familial Alzheimer disease (eoFAD) mutation for the first time in vivo with PET in comparison with other eoFAD mutations and sporadic Alzheimer disease (sAD).Methods: We examined 2 APParc mutation carriers together with 5 noncarrier siblings cross-sectionally with C-11-labeled Pittsburgh compound B (PiB) and F-18-fluorodeoxyglucose (FDG) PET, as well as MRI, CSF biomarkers, and neuropsychological tests. Likewise, we examined 7 patients with sAD, 1 carrier of a presenilin 1 (PSEN1) mutation, 1 carrier of the Swedish APP (APPswe) mutation, and 7 healthy controls (HCs).Results: Cortical PiB retention was very low in the APParc mutation carriers while cerebral glucose metabolism and CSF levels of A beta(1-42), total and phosphorylated tau were clearly pathologic. This was in contrast to the PSEN1 and APPswe mutation carriers revealing high PiB retention in the cortex and the striatum in combination with abnormal glucose metabolism and CSF biomarkers, and the patients with sAD who showed typically high cortical PiB retention and pathologic CSF levels as well as decreased glucose metabolism when compared with HCs.Conclusions: The lack of fibrillar beta-amyloid (A beta) as visualized by PiB PET in APParc mutation carriers suggests, given the reduced glucose metabolism and levels of A beta(1-42) in CSF, that other forms of A beta such as oligomers and protofibrils are important for the pathologic processes leading to clinical Alzheimer disease. Neurology(R) 2012;79:229-236