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Longitudinal (18F)AV-1451 PET imaging in a patient with frontotemporal dementia due to a Q351R MAPT mutation.
Journal of Neurology, Neurosurgery, and Psychiatry ( IF 11.0 ) Pub Date : 2019-08-22 , DOI: 10.1136/jnnp-2019-320904
Rhian S Convery 1 , Jieqing Jiao 2 , Mica T M Clarke 1 , Katrina M Moore 1 , Carolin A M Koriath 1 , Ione O C Woollacott 1 , Philip S J Weston 1 , Roger Gunn 3 , Ilan Rabiner 3 , David M Cash 1 , Martin N Rossor 1 , Jason D Warren 1 , Nick C Fox 1, 4 , Sebastien Ourselin 2 , Martina Bocchetta 1 , Jonathan D Rohrer 5
Affiliation  

Mutations in the microtubule associated protein tau ( MAPT ) gene are a common cause of inherited frontotemporal dementia (FTD) and result in the deposition of pathological tau protein in the brain.1 Tau positron emission tomography (PET) may enhance in vivo diagnosis and testing of tau-based therapies in FTD, however, few tau ligands have been validated in FTD. The (18F)AV-1451 ligand was developed to assess in vivo tau accumulation and has consistently been shown to bind to tau in individuals with Alzheimer’s disease (AD) but less work has focused on the non-AD tauopathies, including FTD. Autoradiography studies of (18F)AV-1451 have shown strong binding in regions of neurofibrillary tangles matching the pattern of paired helical filament (PHF) immunochemistry but have not shown strong binding to non-PHF-tau.2 In (18F)AV-1451 studies conducted in FTD spectrum disorders, not only does the ligand not bind strongly to non-PHF tau, but there is significant in vivo binding reported in conditions where no tau is expected at all, for example, in patients with semantic variant primary progressive aphasia and with C9orf72 expansions where TDP-43 pathology is usually found.3 4 (18F)AV-1451 also displays both off-target binding in the basal ganglia and an age-related increase in binding in cognitively healthy controls.3 Nevertheless, this ligand has shown strong binding in a subset of FTD-causing MAPT mutations, including V337M and R406W that are associated with PHF-tau pathology.1 5 (18F)AV-1451 may therefore be useful in detecting tau pathology in some genetic forms of FTD that result in similar structural conformations of tau to that of AD. Here we describe longitudinal (18F)AV-1451 PET imaging from a patient with FTD due to a Q351R mutation located on exon 12 of the MAPT gene.6 ### Participants A patient with a Q351R MAPT mutation in her mid-60s as …

中文翻译:

因 Q351R MAPT 突变导致额颞叶痴呆患者的纵向 (18F)AV-1451 PET 成像。

微管相关蛋白 tau (MAPT) 基因突变是遗传性额颞叶痴呆 (FTD) 的常见原因,并导致病理性 tau 蛋白在大脑中沉积。1 Tau 正电子发射断层扫描 (PET) 可以增强体内诊断和测试FTD 中基于 tau 的疗法的研究较多,然而,很少有 tau 配体在 FTD 中得到验证。(18F)AV-1451 配体被开发用于评估体内 tau 积累,并且一直被证明可以与阿尔茨海默病 (AD) 患者的 tau 结合,但较少的工作集中在非 AD tau 病(包括 FTD)上。(18F)AV-1451 的放射自显影研究显示,神经原纤维缠结区域具有强结合,与配对螺旋丝 (PHF) 免疫化学模式相匹配,但未显示与非 PHF-tau 的强结合。2 在 (18F)AV-1451 中在 FTD 谱系障碍中进行的研究表明,该配体不仅不会与非 PHF tau 强烈结合,而且在根本不存在 tau 的情况下,例如在患有语义变异原发性进行性失语症的患者中,报告有显着的体内结合以及通常发现 TDP-43 病理学的 C9orf72 扩展。3 4 (18F)AV-1451 还显示出基底神经节中的脱靶结合以及认知健康对照中与年龄相关的结合增加。3 尽管如此,该配体已显示出与 FTD 引起的 MAPT 突变子集的强结合,包括与 PHF-tau 病理学相关的 V337M 和 R406W。1 因此,5 (18F)AV-1451 可能有助于检测某些遗传形式的 FTD 中的 tau 病理学。导致 tau 的结构构象与 AD 相似。在这里,我们描述了一名因 MAPT 基因外显子 12 上的 Q351R 突变而患有 FTD 的患者的纵向 (18F)AV-1451 PET 成像。6 ### 参与者 一名 60 多岁的患有 Q351R MAPT 突变的患者,因为……
更新日期:2019-12-18
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