Involvement of striatal motoric subregions in familial frontotemporal dementia with parkinsonism harboring the C9orf72 repeat expansions

Background 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 is poorly understood. Method To explore roles striatal motor subdivisions in pathogenesis resulting from C9ORF72 repeat expansions FTDP, two patients FTDP one pedigree and seventeen healthy controls were enrolled. participants received clinical interviews underwent neuropsychological assessments, genetic testing, [18F]-fluorodeoxyglucose PET/MRI, [18F]-dihydrotetrabenazine PET/CT. Voxel-wise region interest analysis conducted respect to gray matter volume, metabolism, dopamine transport function between controls, focusing on part striatum according Oxford-GSK-Imanova Striatal Connectivity Atlas. Result Patient 1 presented initial symptom, while patient 2 exhibited behavior disturbance first followed by within year. Both had hexanucleotide expansion detected C9ORF72(>52 repeats). Gray volume atrophy, hypometabolism dysfunction observed areas striatum. Of patients, marked glucose subregion was 1, corresponding atrophy. In addition, presynaptic dopaminergic integrity deteriorated subregions which consistent Conclusion These findings provide evidence that C9orf72 could result degeneration subregion, contributed FTDP.