Loading…

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

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 (G...

Full description

Saved in:
Bibliographic Details
Published in:NPJ Parkinson's Disease 2021-11, Vol.7 (1), p.104-104, Article 104
Main Authors: Lee, Myung Jun, Pak, Kyoungjune, Kim, Han-Kyeol, Nudelman, Kelly N., Kim, Jong Hun, Kim, Yun Hak, Kang, Junho, Baek, Min Seok, Lyoo, Chul Hyoung
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c540t-14efead7ad2b16acfdb2186ad7c934e4937e9443a0342c608cd10501ca31ec533
cites cdi_FETCH-LOGICAL-c540t-14efead7ad2b16acfdb2186ad7c934e4937e9443a0342c608cd10501ca31ec533
container_end_page 104
container_issue 1
container_start_page 104
container_title NPJ Parkinson's Disease
container_volume 7
creator Lee, Myung Jun
Pak, Kyoungjune
Kim, Han-Kyeol
Nudelman, Kelly N.
Kim, Jong Hun
Kim, Yun Hak
Kang, Junho
Baek, Min Seok
Lyoo, Chul Hyoung
description 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.
doi_str_mv 10.1038/s41531-021-00250-2
format article
fullrecord <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_9165daac7d7b4ce4bd09c0766ac5a5ee</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_9165daac7d7b4ce4bd09c0766ac5a5ee</doaj_id><sourcerecordid>2604020373</sourcerecordid><originalsourceid>FETCH-LOGICAL-c540t-14efead7ad2b16acfdb2186ad7c934e4937e9443a0342c608cd10501ca31ec533</originalsourceid><addsrcrecordid>eNp9ks1u1TAQhSMEotWlL8ACRWLDJjD-iZNskFAFpVIlWMDamtiT1JckDnZSibfHaUppWbCwbM18c8b2nCx7yeAtA1G_i5KVghXA0wJeQsGfZKdcVKKooayePjifZGcxHgGASVU3JTzPToSshWpUc5qZC5pocSbv0Cw-xBy7jszipj63fsbRTRT6lLa0UHA-4OL8lNs1bMRyTfkcaPSpMo8L9pT7Lv-K4Yeb4oa5SBjpRfaswyHS2d1-yL5_-vjt_HNx9eXi8vzDVWFKCUvBJHWEtkLLW6bQdLblrFYpYhohSTaiokZKgSAkNwpqYxmUwAwKRqYU4pBd7rrW41HPwY0YfmmPTt8GfOg1hvTWgXTDVGkRTWWrVhqSrYXGQKVS2xJLoqT1ftea13Yka2haAg6PRB9nJnete3-ja8WVrFUSeHMnEPzPleKiRxcNDQNO5NeouQIJHNKQEvr6H_To1zClr9oonsS2WR4yvlMm-BgDdfeXYaA3S-jdEjpZQt9aQvNU9OrhM-5L_hggAWIH4ryNlMLf3v-R_Q1D2cO9</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2602863237</pqid></control><display><type>article</type><title>Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease</title><source>PubMed Central Free</source><source>Publicly Available Content (ProQuest)</source><source>Springer Nature - nature.com Journals - Fully Open Access</source><creator>Lee, Myung Jun ; Pak, Kyoungjune ; Kim, Han-Kyeol ; Nudelman, Kelly N. ; Kim, Jong Hun ; Kim, Yun Hak ; Kang, Junho ; Baek, Min Seok ; Lyoo, Chul Hyoung</creator><creatorcontrib>Lee, Myung Jun ; Pak, Kyoungjune ; Kim, Han-Kyeol ; Nudelman, Kelly N. ; Kim, Jong Hun ; Kim, Yun Hak ; Kang, Junho ; Baek, Min Seok ; Lyoo, Chul Hyoung</creatorcontrib><description>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.</description><identifier>ISSN: 2373-8057</identifier><identifier>EISSN: 2373-8057</identifier><identifier>DOI: 10.1038/s41531-021-00250-2</identifier><identifier>PMID: 34836969</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/617/375/1718 ; 692/617/375/364 ; Biomedical and Life Sciences ; Biomedical research ; Biomedicine ; Demographics ; Dopamine ; Generalized linear models ; Health risk assessment ; Hospitals ; Medicine ; Neurology ; Neurosciences ; Parkinson's disease ; Research centers</subject><ispartof>NPJ Parkinson's Disease, 2021-11, Vol.7 (1), p.104-104, Article 104</ispartof><rights>The Author(s) 2021. corrected publication 2022</rights><rights>2021. The Author(s).</rights><rights>The Author(s) 2021. corrected publication 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2021, corrected publication 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-14efead7ad2b16acfdb2186ad7c934e4937e9443a0342c608cd10501ca31ec533</citedby><cites>FETCH-LOGICAL-c540t-14efead7ad2b16acfdb2186ad7c934e4937e9443a0342c608cd10501ca31ec533</cites><orcidid>0000-0002-0101-6472 ; 0000-0002-7650-6708 ; 0000-0003-2231-672X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2602863237/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2602863237?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34836969$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Myung Jun</creatorcontrib><creatorcontrib>Pak, Kyoungjune</creatorcontrib><creatorcontrib>Kim, Han-Kyeol</creatorcontrib><creatorcontrib>Nudelman, Kelly N.</creatorcontrib><creatorcontrib>Kim, Jong Hun</creatorcontrib><creatorcontrib>Kim, Yun Hak</creatorcontrib><creatorcontrib>Kang, Junho</creatorcontrib><creatorcontrib>Baek, Min Seok</creatorcontrib><creatorcontrib>Lyoo, Chul Hyoung</creatorcontrib><title>Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease</title><title>NPJ Parkinson's Disease</title><addtitle>npj Parkinsons Dis</addtitle><addtitle>NPJ Parkinsons Dis</addtitle><description>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.</description><subject>692/617/375/1718</subject><subject>692/617/375/364</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical research</subject><subject>Biomedicine</subject><subject>Demographics</subject><subject>Dopamine</subject><subject>Generalized linear models</subject><subject>Health risk assessment</subject><subject>Hospitals</subject><subject>Medicine</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Parkinson's disease</subject><subject>Research centers</subject><issn>2373-8057</issn><issn>2373-8057</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9ks1u1TAQhSMEotWlL8ACRWLDJjD-iZNskFAFpVIlWMDamtiT1JckDnZSibfHaUppWbCwbM18c8b2nCx7yeAtA1G_i5KVghXA0wJeQsGfZKdcVKKooayePjifZGcxHgGASVU3JTzPToSshWpUc5qZC5pocSbv0Cw-xBy7jszipj63fsbRTRT6lLa0UHA-4OL8lNs1bMRyTfkcaPSpMo8L9pT7Lv-K4Yeb4oa5SBjpRfaswyHS2d1-yL5_-vjt_HNx9eXi8vzDVWFKCUvBJHWEtkLLW6bQdLblrFYpYhohSTaiokZKgSAkNwpqYxmUwAwKRqYU4pBd7rrW41HPwY0YfmmPTt8GfOg1hvTWgXTDVGkRTWWrVhqSrYXGQKVS2xJLoqT1ftea13Yka2haAg6PRB9nJnete3-ja8WVrFUSeHMnEPzPleKiRxcNDQNO5NeouQIJHNKQEvr6H_To1zClr9oonsS2WR4yvlMm-BgDdfeXYaA3S-jdEjpZQt9aQvNU9OrhM-5L_hggAWIH4ryNlMLf3v-R_Q1D2cO9</recordid><startdate>20211126</startdate><enddate>20211126</enddate><creator>Lee, Myung Jun</creator><creator>Pak, Kyoungjune</creator><creator>Kim, Han-Kyeol</creator><creator>Nudelman, Kelly N.</creator><creator>Kim, Jong Hun</creator><creator>Kim, Yun Hak</creator><creator>Kang, Junho</creator><creator>Baek, Min Seok</creator><creator>Lyoo, Chul Hyoung</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Portfolio</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-0101-6472</orcidid><orcidid>https://orcid.org/0000-0002-7650-6708</orcidid><orcidid>https://orcid.org/0000-0003-2231-672X</orcidid></search><sort><creationdate>20211126</creationdate><title>Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease</title><author>Lee, Myung Jun ; Pak, Kyoungjune ; Kim, Han-Kyeol ; Nudelman, Kelly N. ; Kim, Jong Hun ; Kim, Yun Hak ; Kang, Junho ; Baek, Min Seok ; Lyoo, Chul Hyoung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-14efead7ad2b16acfdb2186ad7c934e4937e9443a0342c608cd10501ca31ec533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>692/617/375/1718</topic><topic>692/617/375/364</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical research</topic><topic>Biomedicine</topic><topic>Demographics</topic><topic>Dopamine</topic><topic>Generalized linear models</topic><topic>Health risk assessment</topic><topic>Hospitals</topic><topic>Medicine</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Parkinson's disease</topic><topic>Research centers</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Myung Jun</creatorcontrib><creatorcontrib>Pak, Kyoungjune</creatorcontrib><creatorcontrib>Kim, Han-Kyeol</creatorcontrib><creatorcontrib>Nudelman, Kelly N.</creatorcontrib><creatorcontrib>Kim, Jong Hun</creatorcontrib><creatorcontrib>Kim, Yun Hak</creatorcontrib><creatorcontrib>Kang, Junho</creatorcontrib><creatorcontrib>Baek, Min Seok</creatorcontrib><creatorcontrib>Lyoo, Chul Hyoung</creatorcontrib><collection>Springer_OA刊</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest_Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>NPJ Parkinson's Disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Myung Jun</au><au>Pak, Kyoungjune</au><au>Kim, Han-Kyeol</au><au>Nudelman, Kelly N.</au><au>Kim, Jong Hun</au><au>Kim, Yun Hak</au><au>Kang, Junho</au><au>Baek, Min Seok</au><au>Lyoo, Chul Hyoung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease</atitle><jtitle>NPJ Parkinson's Disease</jtitle><stitle>npj Parkinsons Dis</stitle><addtitle>NPJ Parkinsons Dis</addtitle><date>2021-11-26</date><risdate>2021</risdate><volume>7</volume><issue>1</issue><spage>104</spage><epage>104</epage><pages>104-104</pages><artnum>104</artnum><issn>2373-8057</issn><eissn>2373-8057</eissn><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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34836969</pmid><doi>10.1038/s41531-021-00250-2</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-0101-6472</orcidid><orcidid>https://orcid.org/0000-0002-7650-6708</orcidid><orcidid>https://orcid.org/0000-0003-2231-672X</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2373-8057
ispartof NPJ Parkinson's Disease, 2021-11, Vol.7 (1), p.104-104, Article 104
issn 2373-8057
2373-8057
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_9165daac7d7b4ce4bd09c0766ac5a5ee
source PubMed Central Free; Publicly Available Content (ProQuest); Springer Nature - nature.com Journals - Fully Open Access
subjects 692/617/375/1718
692/617/375/364
Biomedical and Life Sciences
Biomedical research
Biomedicine
Demographics
Dopamine
Generalized linear models
Health risk assessment
Hospitals
Medicine
Neurology
Neurosciences
Parkinson's disease
Research centers
title Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T07%3A20%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20factors%20affecting%20dopaminergic%20deterioration%20during%20the%20premotor%20stage%20of%20Parkinson%20disease&rft.jtitle=NPJ%20Parkinson's%20Disease&rft.au=Lee,%20Myung%20Jun&rft.date=2021-11-26&rft.volume=7&rft.issue=1&rft.spage=104&rft.epage=104&rft.pages=104-104&rft.artnum=104&rft.issn=2373-8057&rft.eissn=2373-8057&rft_id=info:doi/10.1038/s41531-021-00250-2&rft_dat=%3Cproquest_doaj_%3E2604020373%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c540t-14efead7ad2b16acfdb2186ad7c934e4937e9443a0342c608cd10501ca31ec533%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2602863237&rft_id=info:pmid/34836969&rfr_iscdi=true