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• W2758379647 abstract "ABSTRACT Background A number of genetic loci are associated with risk for Parkinson's disease (PD) based on genome‐wide association studies; however, the relationship between genetic variants and nigrostriatal degeneration, which is the structural correlate of parkinsonism, has not been reported. Objectives We quantified nigrostriatal dopaminergic integrity with image analysis of putaminal tyrosine hydroxylase immunoreactivity in 492 brains with Lewy body disease and used this pathologic endophenotype to explore possible association with PD genetic variants. Methods The study cases had Lewy‐related pathology and variable degrees of nigrostriatal degeneration. They were assigned to one of the following clinical subgroups according to their predominant clinical syndrome: parkinsonism‐predominant, parkinsonism+dementia, and dementia‐predominant. In addition to putaminal tyrosine hydroxylase immunoreactivity, semiquantitative scoring was used to assess substantia nigra neuronal loss. A total of 29 PD genetic risk variants were genotyped on each case. Results When compared with controls, tyrosine hydroxylase immunoreactivity was reduced in Lewy body cases in the dorsolateral (79%) and ventromedial (57%) putamen. The dorsolateral region was better preserved in dementia‐predominant cases than in cases with parkinsonism. Dorsolateral putaminal tyrosine hydroxylase immunoreactivity correlated with neuronal loss in the ventrolateral substantia nigra. Genetic analyses showed no significant association of PD risk variants with putaminal tyrosine hydroxylase immunoreactivity. Conclusions The results confirm regional differences in putaminal dopaminergic degeneration and vulnerability of nigrostriatal pathway in Lewy body disorders with parkinsonism. The lack of association with PD genetic risk variants suggests that they may not be associated with quantitative endophenotypes of nigrostriatal degeneration, but more likely related to the risk of disease per se. © 2017 International Parkinson and Movement Disorder Society" @default.
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• W2758379647 date "2017-09-26" @default.
• W2758379647 modified "2023-10-15" @default.
• W2758379647 title "Regional analysis and genetic association of nigrostriatal degeneration in Lewy body disease" @default.
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• W2758379647 doi "https://doi.org/10.1002/mds.27184" @default.
• W2758379647 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5915345" @default.
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