Deters Kacie D, Risacher Shannon L, Farlow Martin R, Unverzagt Frederick W, Kareken David A, Hutchins Gary D, Yoder Karmen K, Murrell Jill R, Spina Salvatore, Epperson Francine, Gao Sujuan, Saykin Andrew J, Ghetti Bernardino
Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, IN, USA ; Indiana Alzheimer Disease Center, Indiana University School of Medicine Indianapolis, IN, USA ; Program in Medical Neuroscience, Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine Indianapolis, IN, USA.
Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, IN, USA ; Indiana Alzheimer Disease Center, Indiana University School of Medicine Indianapolis, IN, USA.
Am J Neurodegener Dis. 2014 Dec 5;3(3):103-14. eCollection 2014.
Multiple systems tauopathy with presenile dementia (MSTD), a form of frontotemporal dementia with parkinsonism-17 with tau inclusions (FTDP-17T), is a neurodegenerative disorder caused by an (a) to (g) transition at position +3 of intron 10 of the microtubule associated protein tau (MAPT) gene. The mutation causes overexpression of 4 repeat (4R) tau isoforms with increased 4R/3R ratio leading to neurodegeneration. Clinically, these patients primarily present with behavioral variant FTD (bvFTD) and show disinhibition, disordered social comportment, and impaired executive function, memory, and speech. While altered glucose metabolism has been reported in subjects with sporadic bvFTD, it has yet to be investigated in an FTDP-17 sample of this size. In this study, eleven mutation carriers (5 males; mean age = 48.0 ± 6.9 years) and eight non-carriers (2 males; mean age = 43.7 ± 12.0 years) from a MSTD family were imaged using [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Eight of the MAPT intron 10 +3 mutation carriers met diagnostic criteria for bvFTD at the time of the PET scan, while three MAPT intron 10 +3 carriers were not cognitively impaired at the time of scan. Non-carriers had no clinically-relevant cognitive impairment at the time of the PET scan. Additionally, ten mutation carriers (5 males; mean age = 48.04 ± 2.1 years) and seven non-carriers (2 males; mean age 46.1 ± 4.1 years) underwent magnetic resonance imaging (MRI) which is an expanded sample size from a previous study. Seven MAPT mutation carriers met diagnostic criteria for bvFTD at the time of the MRI scan. Images were assessed on a voxel-wise basis for the effect of mutation carrier status. SPM8 was used for preprocessing and statistical analyses. Compared to non-carriers, MAPT mutation carriers showed lower [(18)F]FDG uptake bilaterally in the medial temporal lobe, and the parietal and frontal cortices. Anatomical changes were predominantly seen bilaterally in the medial temporal lobe areas which substantially overlapped with the hypometabolism findings. These anatomical and metabolic changes overlap previously described patterns of neurodegeneration in MSTD patients and are consistent with the characteristics of their cognitive dysfunction. These results suggest that neuroimaging can describe the neuropathology associated with this MAPT mutation.
伴早老性痴呆的多系统tau蛋白病（MSTD）是额颞叶痴呆伴帕金森综合征-17型（FTDP-17T）的一种形式，是由微管相关蛋白tau（MAPT）基因第10内含子+3位的（a）到（g）转换引起的神经退行性疾病。该突变导致4重复（4R）tau异构体过度表达，4R/3R比率增加，从而导致神经退行性变。临床上，这些患者主要表现为行为变异型额颞叶痴呆（bvFTD），表现为脱抑制、社交行为紊乱以及执行功能、记忆和言语受损。虽然在散发性bvFTD患者中已报道有葡萄糖代谢改变，但在这种规模的FTDP-17样本中尚未进行研究。在本研究中，对一个MSTD家族的11名突变携带者（5名男性；平均年龄=48.0±6.9岁）和8名非携带者（2名男性；平均年龄=43.7±12.0岁）进行了[（18）F]氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）成像。8名MAPT第10内含子+3突变携带者在PET扫描时符合bvFTD的诊断标准，而3名MAPT第10内含子+3携带者在扫描时无认知障碍。非携带者在PET扫描时无临床相关的认知障碍。此外，10名突变携带者（5名男性；平均年龄=48.04±2.1岁）和7名非携带者（2名男性；平均年龄46.1±4.1岁）接受了磁共振成像（MRI）检查，这是对先前研究样本量的扩大。7名MAPT突变携带者在MRI扫描时符合bvFTD的诊断标准。基于体素对图像进行评估，以分析突变携带者状态的影响。使用SPM8进行预处理和统计分析。与非携带者相比，MAPT突变携带者双侧内侧颞叶、顶叶和额叶皮质的[（18）F]FDG摄取较低。解剖学变化主要双侧出现在内侧颞叶区域，并与代谢减低的发现有很大重叠。这些解剖学和代谢变化与先前描述的MSTD患者神经退行性变模式重叠，并且与其认知功能障碍的特征一致。这些结果表明，神经影像学可以描述与这种MAPT突变相关的神经病理学。
