Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Suite 10.014, Charlestown, Boston, MA, 02119, USA.
Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
Alzheimers Res Ther. 2019 Feb 4;11(1):17. doi: 10.1186/s13195-019-0468-1.
Autosomal dominant Alzheimer's disease (ADAD) is distinguished from late-onset AD by early striatal amyloid-β deposition. To determine whether striatal Pittsburgh compound B (PiB)-PET measurements of amyloid-β can help predict disease severity in ADAD, we compared relationships of striatal and neocortical PiB-PET to age, tau-PET, and memory performance in the Colombian Presenilin 1 E280A kindred.
Fourteen carriers (age = 28-42, Mini-Mental State Examination = 26-30) and 20 age-matched non-carriers were evaluated using PiB, flortaucipir (FTP; tau), and memory testing (CERAD Word List Learning). PiB-PET signal was measured in neocortical and striatal aggregates. FTP-PET signal was measured in entorhinal cortex.
Compared to non-carriers, mutation carriers had age-related elevations in both neocortical and striatal PiB binding. The PiB elevation in carriers was significantly greater in the striatum than in the neocortex. In mutation carriers, PiB binding in both the neocortex and the striatum is related to entorhinal FTP; however, the association was stronger with the striatum. Only striatal PiB was associated with worse memory. Remarkably, PiB binding in the striatum, but not in the neocortex, predicted entorhinal FTP and lower memory scores after adjusting for age, indicating that striatal PiB identified the carriers with the most severe disease.
Based on these preliminary cross-sectional findings, striatal PiB-PET measurements may offer particular value in the detection and tracking of preclinical ADAD, informing a mutation carrier's prognosis and evaluating amyloid-β-modifying ADAD treatments.
常染色体显性阿尔茨海默病（ADAD）的特征是早期纹状体淀粉样蛋白-β沉积，与晚发性 AD 不同。为了确定纹状体匹兹堡化合物 B（PiB）-正电子发射断层扫描（PET）测量的淀粉样蛋白-β是否有助于预测 ADAD 的疾病严重程度，我们比较了纹状体和新皮质 PiB-PET 与年龄、tau-PET 和哥伦比亚早老素 1 E280A 家族记忆表现的关系。
14 名携带者（年龄=28-42，简易精神状态检查=26-30）和 20 名年龄匹配的非携带者接受了 PiB、氟曲替酯（FTP；tau）和记忆测试（CERAD 单词列表学习）。在新皮质和纹状体聚集物中测量 PiB-PET 信号。在内嗅皮层测量 FTP-PET 信号。
与非携带者相比，突变携带者的新皮质和纹状体 PiB 结合均随年龄增长而升高。与新皮质相比，携带者的纹状体 PiB 升高更为显著。在突变携带者中，新皮质和纹状体的 PiB 结合与内嗅皮层的 FTP 相关；然而，与纹状体的相关性更强。只有纹状体的 PiB 与记忆较差相关。值得注意的是，纹状体 PiB 结合，而不是新皮质 PiB 结合，可预测内嗅皮层的 FTP 和较低的记忆评分，这表明纹状体 PiB 可识别疾病最严重的携带者。
基于这些初步的横断面研究结果，纹状体 PiB-PET 测量可能在 ADAD 的早期检测和跟踪中具有特殊价值，为突变携带者的预后提供信息，并评估 ADAD 的淀粉样蛋白-β修饰治疗效果。
