期刊
NPJ PARKINSONS DISEASE
卷 8, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41531-022-00398-5
关键词
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资金
- National Natural Science Foundation of China [81971011, 81901285]
- Ministry of Science and Technology of China [2019YFC0118600]
- Beijing Municipal Science and Technology Committee [D171100008217005, 7202060]
- Beijing Postdoctoral Research Foundation [2020-ZZ-016]
This study investigated the pathophysiological mechanism of parkinsonism caused by C9ORF72 repeat expansions in frontotemporal dementia with parkinsonism (FTDP). Clinical and imaging analysis of two FTDP patients and seventeen healthy controls revealed gray matter volume atrophy, hypometabolism, and dopamine dysfunction in the motor areas of the striatum. These findings suggest that C9ORF72 repeat expansions may contribute to the degeneration and dopaminergic dysfunction of the striatal motor subregion in FTDP patients with parkinsonism.
The chromosome 9 open reading frame 72 (C9ORF72) has been proposed as the causative gene of frontotemporal dementia with parkinsonism (FTDP), but its pathophysiological mechanism of parkinsonism is poorly understood. To explore the roles of striatal motor subdivisions in the pathogenesis of parkinsonism resulting from C9ORF72 repeat expansions in the FTDP, two patients with FTDP from one pedigree and seventeen healthy controls were enrolled. The participants received clinical interviews, physical examinations, genetic testing, [F-18]-fluorodeoxyglucose PET/MRI, and [F-18]-dihydrotetrabenazine PET/CT. Voxel-wise and region of interest analysis were conducted with respect to gray matter volume, metabolism, and dopamine transport function between patients and controls, focusing on the motor part of the striatum according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. Patient 1 presented with parkinsonism as the initial symptom, while patient 2 exhibited behavior disturbance as the first symptom, followed by parkinsonism within one year. Both patients had the hexanucleotide expansion detected in C9ORF72(>52 repeats). Gray matter volume atrophy, hypometabolism and dopamine dysfunction were observed in the motor areas of the striatum. Of the two patients, marked glucose hypometabolism within the striatal motor subregion was observed in patient 1, with corresponding gray matter atrophy. In addition, presynaptic dopaminergic integrity of patient 2 was deteriorated in the motor subregions which was consistent with gray matter atrophy. These findings imply that parkinsonism in FTDP may be associated with the degeneration and dopaminergic dysfunction of the striatal motor subregion, which might be attributed to C9orf72 repeat expansions.
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