Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease

Abstract To estimate dopaminergic dysfunction in patients with Parkinson disease (PD) during the premotor stage and to investigate the effect of genetic factors on the trajectories. Using longitudinal dopamine transporter single-photon emission computed tomography data from 367 sporadic PD (sPD), 72...

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Autores principales:	Myung Jun Lee, Kyoungjune Pak, Han-Kyeol Kim, Kelly N. Nudelman, Jong Hun Kim, Yun Hak Kim, Junho Kang, Min Seok Baek, Chul Hyoung Lyoo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/9165daac7d7b4ce4bd09c0766ac5a5ee
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spelling	oai:doaj.org-article:9165daac7d7b4ce4bd09c0766ac5a5ee2021-11-28T12:23:18ZGenetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease10.1038/s41531-021-00250-22373-8057https://doaj.org/article/9165daac7d7b4ce4bd09c0766ac5a5ee2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41531-021-00250-2https://doaj.org/toc/2373-8057Abstract To estimate dopaminergic dysfunction in patients with Parkinson disease (PD) during the premotor stage and to investigate the effect of genetic factors on the trajectories. Using longitudinal dopamine transporter single-photon emission computed tomography data from 367 sporadic PD (sPD), 72 LRRK2 (G2019S), and 39 GBA (N370S) PD patients in the Parkinson’s Progression Markers Initiative (PPMI) study, we estimated the temporal trajectories of putaminal-specific binding ratios using an integrating function between baseline values and their annual change rates. In order to test reproducibility, we computed another trajectory for sPD using positron emission tomography data of 38 sPD patients at Gangnam Severance Hospital (GSH). Temporal trajectories of sPD were compared between the groups separated by age at onset (AAO) and polygenic load for common PD risk variants, and also compared with genetic PD. sPD patients in both the PPMI and GSH cohorts showed similar onset of dopaminergic degeneration around 10 years before motor onset. Early-onset PD patients exhibited later onset of degeneration and a faster decline in dopaminergic activity during the premotor period than late-onset patients. sPD patients with high polygenic load were associated with earlier onset and slower progression of dopaminergic dysfunction. Compared to the sPD and LRRK2 PD groups, GBA PD patients exhibited faster deterioration of dopaminergic function during the premotor stage. Dopaminergic dysfunction in PD appears to start about 10 years before motor onset. Genetic factors may be contributing to the heterogeneity of dopaminergic deterioration during the premotor stage.Myung Jun LeeKyoungjune PakHan-Kyeol KimKelly N. NudelmanJong Hun KimYun Hak KimJunho KangMin Seok BaekChul Hyoung LyooNature PortfolioarticleNeurology. Diseases of the nervous systemRC346-429ENnpj Parkinson's Disease, Vol 7, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurology. Diseases of the nervous system RC346-429 Myung Jun Lee Kyoungjune Pak Han-Kyeol Kim Kelly N. Nudelman Jong Hun Kim Yun Hak Kim Junho Kang Min Seok Baek Chul Hyoung Lyoo Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease
description	Abstract To estimate dopaminergic dysfunction in patients with Parkinson disease (PD) during the premotor stage and to investigate the effect of genetic factors on the trajectories. Using longitudinal dopamine transporter single-photon emission computed tomography data from 367 sporadic PD (sPD), 72 LRRK2 (G2019S), and 39 GBA (N370S) PD patients in the Parkinson’s Progression Markers Initiative (PPMI) study, we estimated the temporal trajectories of putaminal-specific binding ratios using an integrating function between baseline values and their annual change rates. In order to test reproducibility, we computed another trajectory for sPD using positron emission tomography data of 38 sPD patients at Gangnam Severance Hospital (GSH). Temporal trajectories of sPD were compared between the groups separated by age at onset (AAO) and polygenic load for common PD risk variants, and also compared with genetic PD. sPD patients in both the PPMI and GSH cohorts showed similar onset of dopaminergic degeneration around 10 years before motor onset. Early-onset PD patients exhibited later onset of degeneration and a faster decline in dopaminergic activity during the premotor period than late-onset patients. sPD patients with high polygenic load were associated with earlier onset and slower progression of dopaminergic dysfunction. Compared to the sPD and LRRK2 PD groups, GBA PD patients exhibited faster deterioration of dopaminergic function during the premotor stage. Dopaminergic dysfunction in PD appears to start about 10 years before motor onset. Genetic factors may be contributing to the heterogeneity of dopaminergic deterioration during the premotor stage.
format	article
author	Myung Jun Lee Kyoungjune Pak Han-Kyeol Kim Kelly N. Nudelman Jong Hun Kim Yun Hak Kim Junho Kang Min Seok Baek Chul Hyoung Lyoo
author_facet	Myung Jun Lee Kyoungjune Pak Han-Kyeol Kim Kelly N. Nudelman Jong Hun Kim Yun Hak Kim Junho Kang Min Seok Baek Chul Hyoung Lyoo
author_sort	Myung Jun Lee
title	Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease
title_short	Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease
title_full	Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease
title_fullStr	Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease
title_full_unstemmed	Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease
title_sort	genetic factors affecting dopaminergic deterioration during the premotor stage of parkinson disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9165daac7d7b4ce4bd09c0766ac5a5ee
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_version_	1718408028771844096

Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease

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