The Role of Striatal Subdivisions in FTDP Explained

Published on April 15, 2022

Imagine the brain is a bustling city, and the striatum is an important neighborhood within it. In this neighborhood, researchers have discovered that a certain gene mutation can lead to a condition called frontotemporal dementia with parkinsonism (FTDP). By examining a patient with this mutation, the scientists learned that specific areas within the striatum are affected differently. The patient experienced severe reductions in metabolism and dopamine transport function in the limbic and executive subregions, while the rostral and caudal motor subregions were relatively spared. This suggests that cognitive impairment in FTDP may be linked to alterations in frontal striatal loops, while the development of parkinsonism could be primarily due to disturbances in presynaptic nigrostriatal loops influenced by the PRNP V180I mutation. These findings open up new avenues for understanding the complex interplay between different regions of the striatum and neurodegenerative disorders like FTDP. To dive deeper into this fascinating research, check out the full article!

ObjectiveTo explore the roles of striatal subdivisions in the pathogenesis of frontotemporal dementia with parkinsonism (FTDP) in a patient resulting from prion protein gene (PRNP) mutation.MethodsThis patient received clinical interviews and underwent neuropsychological assessments, genetic testing, [18F]-fluorodeoxyglucose positron emission tomography ([18F]-FDG PET)/MRI, and [18F]-dihydrotetrabenazine positron emission tomography ([18F]-DTBZ PET)/CT. Region-of-interest analysis was conducted concerning metabolism, and dopamine transport function between this patient and 12 controls, focusing on the striatum subregions according to the Oxford-GSK-Imanova Striatal Connectivity Atlas.ResultsA 64-year-old man initially presented with symptoms of motor dysfunction and subsequently behavioral and personality changes. FTDP was initially suspected. Sequence analysis disclosed a valine to isoleucine at codon 180 in PRNP. Compared to controls, this patient had a severe reduction (> 2SD) of standard uptake value ratio (SUVR) in the limbic and executive subregions but relative retention of metabolism in rostral motor and caudal motor subregions using [18F]-FDG PET/MRI, and the SUVR decreased significantly across the striatal in [18F]-DTBZ PET/CT, especially in the rostral motor and caudal motor subregions.ConclusionThe alteration of frontal striatal loops may be involved in cognitive impairment in FTDP, and the development of parkinsonism in FTDP may be primarily due to the involvement of the presynaptic nigrostriatal loops in PRNP V180I mutation.

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