Frontotemporal dementia with the V337M MAPT mutation
Frontotemporal dementia with the V337M MAPT mutation
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DOI：
10.1212/wnl.0000000000003636
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发表时间：
2017-02
期刊：
影响因子：
9.9
通讯作者：
S. Spina;Daniel R. Schonhaut;B. Boeve;W. Seeley;R. Ossenkoppele;J. O’Neil;Andreas Lazaris;H. Rosen;A. Boxer;D. Perry;B. Miller;D. Dickson;J. Parisi;W. Jagust;M. Murray;G. Rabinovici
中科院分区：
文献类型：
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作者：
S. Spina;Daniel R. Schonhaut;B. Boeve;W. Seeley;R. Ossenkoppele;J. O’Neil;Andreas Lazaris;H. Rosen;A. Boxer;D. Perry;B. Miller;D. Dickson;J. Parisi;W. Jagust;M. Murray;G. Rabinovici
目的：评价V337M微管相关蛋白tau(MAPT)突变相关的额颞叶痴呆(FTD)患者体内应用[18F]AV1451正电子发射计算机断层显像(PET)的tau病变。方法：MAPT突变与过度磷酸化的tau蛋白在神经元和胶质细胞中沉积有关。PET示踪剂[18F]AV1451与阿尔茨海默病(AD)中由神经纤维缠结组成的成对螺旋细丝tau具有高亲和力，而尸检研究表明，大多数非AD tauopathy的tau细丝结合较低或不结合。我们描述了临床、结构MRI和V337M MAPT突变携带者中受FTD影响的[18F]AV1451 PET表现，以及他的患病母亲和另一名同样受FTD影响的无关V337M MAPT携带者的病理结果。AD患者中成对的螺旋微丝tau和MAPT V337M之间的生化相似性表明，与此突变相关的tau病理构成了[18F]AV1451成像的一个引人注目的靶点。结果：我们发现先证者[18F]AV1451示踪剂在先证者中的滞留程度以及先证者母亲和无关的V337M突变携带者的tau病理在脑内的分布与地形有很强的相关性。我们还发现，根据结构脑MRI和[18F]AV1451PET的评估，先证者的临床表现与局部脑萎缩和tau堆积的程度之间存在显著的相关性和[18F]AV1451结合的程度。结论：我们的研究支持用[18F]AV1451来表征至少一个致病MAPT突变子集的tau病理。
Objective: To assess the efficacy of [18F]AV1451 PET in visualizing tau pathology in vivo in a patient with frontotemporal dementia (FTD) associated with the V337M microtubule-associated protein tau (MAPT) mutation. Methods: MAPT mutations are associated with the deposition of hyperphosphorylated tau protein in neurons and glia. The PET tracer [18F]AV1451 binds with high affinity to paired helical filaments tau that comprises neurofibrillary tangles in Alzheimer disease (AD), while postmortem studies suggest lower or absent binding to the tau filaments of the majority of non-AD tauopathies. We describe clinical, structural MRI, and [18F]AV1451 PET findings in a V337M MAPT mutation carrier affected by FTD and pathologic findings in his affected mother and in an unrelated V337M MAPT carrier also affected with FTD. The biochemical similarity between paired helical filament tau in AD and MAPT V337M predicts that the tau pathology associated with this mutation constitutes a compelling target for [18F]AV1451 imaging. Results: We found a strong association between topography and degree of [18F]AV1451 tracer retention in the proband and distribution of tau pathology in the brain of the proband's mother and the unrelated V337M mutation carrier. We also found a significant correlation between the degree of regional MRI brain atrophy and the extent of [18F]AV1451 binding in the proband and a strong association between the proband's clinical presentation and the extent of regional brain atrophy and tau accumulation as assessed by structural brain MRI and [18F]AV1451PET. Conclusion: Our study supports the usefulness of [18F]AV1451 to characterize tau pathology in at least a subset of pathogenic MAPT mutations.