Jones David T, Townley Ryan A, Graff-Radford Jonathan, Botha Hugo, Knopman David S, Petersen Ronald C, Jack Clifford R, Lowe Val J, Boeve Bradley F
Department of Neurology (D.T.J., R.A.T., J.G.-R., H.B., D.S.K., R.C.P., B.F.B.) and Department of Radiology (D.T.J., C.R.J., V.J.L.), Mayo Clinic, Rochester, MN.
Neurol Genet. 2018 Dec 3;4(6):e290. doi: 10.1212/NXG.0000000000000290. eCollection 2018 Dec.
To study the in vivo binding properties of F-AV-1451 (tau-PET) and Pittsburgh compound B (PiB-PET) in a unique kindred with a familial prion disorder known to produce amyloid plaques composed of prion protein alongside Alzheimer disease (AD)-like tau tangles.
A case series of 4 symptomatic family members with the 12-octapeptide repeat insertion in the gene were imaged with 3T MRI, PiB-PET, and tau-PET in their fourth decade of life.
There was significant neocortical uptake of the tau-PET tracer in all 4 familial prion cases. However, PiB-PET images did not demonstrate abnormally elevated signal in neocortical or cerebellar regions for any of the patients.
In vivo detection of molecular hallmarks of neurodegenerative diseases will be a prerequisite to well-conducted therapeutic trials. Understanding the in vivo behavior of these PET biomarkers in the setting of various neurodegenerative processes is imperative to their proper use in such trials and for research studies focused on the basic neurobiology of neurodegeneration. This study supports the high specificity of neocortical F-AV-1451 binding to AD-like tau and the lack of PiB binding to PrP plaques. It is uncertain how early in the disease course tau pathology appears in the brains of individuals who carry this gene mutation or how it evolves throughout the disease course, but future longitudinal F-AV-1451 imaging of symptomatic and asymptomatic individuals in this kindred will help address these uncertainties.
在一个患有家族性朊病毒病的独特家系中研究F-AV-1451（tau正电子发射断层扫描）和匹兹堡化合物B（PiB正电子发射断层扫描）的体内结合特性，该家系已知会产生由朊病毒蛋白组成的淀粉样斑块以及类似阿尔茨海默病（AD）的tau缠结。
对4名有症状的家族成员进行病例系列研究，这些成员在 基因中有12个八肽重复插入，在其生命的第四个十年接受了3T磁共振成像（MRI）、PiB正电子发射断层扫描和tau正电子发射断层扫描。
在所有4例家族性朊病毒病例中，tau正电子发射断层扫描示踪剂均在新皮质有显著摄取。然而，对于任何患者，PiB正电子发射断层扫描图像在新皮质或小脑区域均未显示异常升高的信号。
体内检测神经退行性疾病的分子特征将是进行良好治疗试验的先决条件。了解这些正电子发射断层扫描生物标志物在各种神经退行性过程中的体内行为对于它们在此类试验中的正确使用以及对于专注于神经退行性变基础神经生物学的研究至关重要。本研究支持新皮质F-AV-1451与类似AD的tau结合的高特异性以及PiB与PrP斑块不结合。携带该基因突变的个体大脑中tau病理学在疾病进程中出现的时间有多早以及它在整个疾病进程中如何演变尚不确定，但未来对该家系中有症状和无症状个体进行纵向F-AV-1451成像将有助于解决这些不确定性。
