Striatal amyloid is associated with tauopathy and memory decline in familial Alzheimer's disease
Striatal amyloid is associated with tauopathy and memory decline in familial Alzheimer's disease
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DOI：
10.1186/s13195-019-0468-1
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发表时间：
2019-02-04
影响因子：
9
通讯作者：
Quiroz, Yakeel T.
中科院分区：
文献类型：
--
作者：
Hanseeuw, Bernard J.;Lopera, Francisco;Quiroz, Yakeel T.
研究背景常染色体显性阿尔茨海默病（autosomaldominantAlzheimer 'sdisease，ADAD）与晚发性AD的区别在于早期纹状体淀粉样蛋白沉积.为了确定纹状体匹兹堡化合物B（PiB）-淀粉样蛋白的PET测量-是否可以帮助预测ADAD的疾病严重程度，我们比较了哥伦比亚早老素1 E280 A家族中纹状体和新皮质PiB-PET与年龄、tau-PET和记忆表现的关系。使用PiB、flortaucipir（FTP; tau）和记忆测试（CERAD单词列表学习）评估了10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。在新皮质和纹状体聚集体中测量PiB-PET信号。FTP-PET信号测量在内嗅cortex.ResultsCompared非运营商，突变运营商有年龄相关的海拔在新皮层和纹状体PiB结合。携带者的PiB升高在纹状体比在新皮层显著更大。在突变携带者中，新皮质和纹状体中的PiB结合与内嗅FTP相关;然而，与纹状体的关联更强。只有纹状体PiB与记忆力下降有关。值得注意的是，在纹状体，但不是在新皮层，预测内嗅FTP和较低的记忆分数调整年龄后，表明纹状体PiB确定的载体与最严重的diseases.ConclusionsBased上这些初步的横截面研究结果，纹状体PiB-PET测量可能提供特殊的价值，在检测和跟踪临床前ADAD，告知突变携带者的预后和评估淀粉样蛋白修饰ADAD治疗。
BackgroundAutosomal dominant Alzheimer's disease (ADAD) is distinguished from late-onset AD by early striatal amyloid- deposition. To determine whether striatal Pittsburgh compound B (PiB)-PET measurements of amyloid- 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.MethodsFourteen 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.ResultsCompared 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.ConclusionsBased 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--modifying ADAD treatments.