Dopaminergic denervation and associated MRI microstructural changes in the nigrostriatal projection in early Parkinson's disease patients

Loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and a profound reduction of striatal dopamine are two hallmarks of Parkinson's disease (PD). However, it's unclear whether degeneration starts at the neuronal soma or the striatal presynaptic terminals, and how micros...

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Autores: López-Aguirre, Miguel, Matarazzo, Michele, Blesa, Javier, Monje, Mariana, Rodríguez-Rojas, Rafael, Sánchez-Ferro, Álvaro, Obeso, José, Pineda-Pardo, José A.
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Universidad Camilo José Cela (UCJC)
Repositorio:Depósito Digital e-UCJC
OAI Identifier:oai:repositorio.ucjc.edu:20.500.12020/1559
Acesso em linha:https://www.nature.com/articles/s41531-023-00586-x
http://hdl.handle.net/20.500.12020/1559
https://doi.org/10.1038/s41531-023-00586-x
Access Level:acceso abierto
Palavra-chave:Ciencias Biomédicas
Parkinson's Disease
PET
Iron
Substantia Nigra
32 Ciencias Médicas
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spelling Dopaminergic denervation and associated MRI microstructural changes in the nigrostriatal projection in early Parkinson's disease patientsLópez-Aguirre, MiguelMatarazzo, MicheleBlesa, JavierMonje, MarianaRodríguez-Rojas, RafaelSánchez-Ferro, ÁlvaroObeso, JoséPineda-Pardo, José A.Ciencias BiomédicasParkinson's DiseasePETIronSubstantia Nigra32 Ciencias MédicasLoss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and a profound reduction of striatal dopamine are two hallmarks of Parkinson's disease (PD). However, it's unclear whether degeneration starts at the neuronal soma or the striatal presynaptic terminals, and how microstructural degeneration is linked to dopaminergic loss is also uncertain. In this study, thirty de novo PD patients and twenty healthy subjects (HS) underwent 6-[18F]-fluoro-L-dopa (FDOPA) PET and MRI studies no later than 12 months from clinical diagnosis. FDOPA uptake rate (Ki), fractional volume of free-water (FW), and iron-sensitive R2* relaxometry were quantified within nigrostriatal regions. Inter-group differences (PD vs HS) were studied using non-parametric statistics and complemented with Cohen's d effect sizes and Bayesian statistics. Correlation analyses were performed exploring biomarker dependencies and their association with bradykinesia scores. PD patients exhibited a significant decline in nigrostriatal dopaminergic activity, being post-commissural putamen (-67%) and posterolateral SNc (-11.7%) the most affected subregions within striatum and SNc respectively. Microstructural alterations (FW) were restricted to the hemisphere corresponding to the most affected side and followed similar spatial gradients as FDOPA Ki (+20% in posterior putamen and +11% in posterolateral SNc). R2* revealed no relevant significant changes. FDOPA and FW were correlated within the posterolateral SNc, and clinical severity was associated with FDOPA Ki loss. The asymmetry between striatal and SNc changes for both dopaminergic depletion and microstructural degeneration biomarkers is consistent with a neurodegenerative process that begins in the striatal terminals before progressing toward the cell bodies in the SNc.Nature Research2023info:eu-repo/semantics/articlehttps://www.nature.com/articles/s41531-023-00586-xhttp://hdl.handle.net/20.500.12020/1559https://doi.org/10.1038/s41531-023-00586-xreponame:Depósito Digital e-UCJCinstname:Universidad Camilo José Cela (UCJC)Inglésinfo:eu-repo/semantics/openAccessoai:repositorio.ucjc.edu:20.500.12020/15592026-05-27T07:36:51Z
dc.title.none.fl_str_mv Dopaminergic denervation and associated MRI microstructural changes in the nigrostriatal projection in early Parkinson's disease patients
title Dopaminergic denervation and associated MRI microstructural changes in the nigrostriatal projection in early Parkinson's disease patients
spellingShingle Dopaminergic denervation and associated MRI microstructural changes in the nigrostriatal projection in early Parkinson's disease patients
López-Aguirre, Miguel
Ciencias Biomédicas
Parkinson's Disease
PET
Iron
Substantia Nigra
32 Ciencias Médicas
title_short Dopaminergic denervation and associated MRI microstructural changes in the nigrostriatal projection in early Parkinson's disease patients
title_full Dopaminergic denervation and associated MRI microstructural changes in the nigrostriatal projection in early Parkinson's disease patients
title_fullStr Dopaminergic denervation and associated MRI microstructural changes in the nigrostriatal projection in early Parkinson's disease patients
title_full_unstemmed Dopaminergic denervation and associated MRI microstructural changes in the nigrostriatal projection in early Parkinson's disease patients
title_sort Dopaminergic denervation and associated MRI microstructural changes in the nigrostriatal projection in early Parkinson's disease patients
dc.creator.none.fl_str_mv López-Aguirre, Miguel
Matarazzo, Michele
Blesa, Javier
Monje, Mariana
Rodríguez-Rojas, Rafael
Sánchez-Ferro, Álvaro
Obeso, José
Pineda-Pardo, José A.
author López-Aguirre, Miguel
author_facet López-Aguirre, Miguel
Matarazzo, Michele
Blesa, Javier
Monje, Mariana
Rodríguez-Rojas, Rafael
Sánchez-Ferro, Álvaro
Obeso, José
Pineda-Pardo, José A.
author_role author
author2 Matarazzo, Michele
Blesa, Javier
Monje, Mariana
Rodríguez-Rojas, Rafael
Sánchez-Ferro, Álvaro
Obeso, José
Pineda-Pardo, José A.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Biomédicas
Parkinson's Disease
PET
Iron
Substantia Nigra
32 Ciencias Médicas
topic Ciencias Biomédicas
Parkinson's Disease
PET
Iron
Substantia Nigra
32 Ciencias Médicas
description Loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and a profound reduction of striatal dopamine are two hallmarks of Parkinson's disease (PD). However, it's unclear whether degeneration starts at the neuronal soma or the striatal presynaptic terminals, and how microstructural degeneration is linked to dopaminergic loss is also uncertain. In this study, thirty de novo PD patients and twenty healthy subjects (HS) underwent 6-[18F]-fluoro-L-dopa (FDOPA) PET and MRI studies no later than 12 months from clinical diagnosis. FDOPA uptake rate (Ki), fractional volume of free-water (FW), and iron-sensitive R2* relaxometry were quantified within nigrostriatal regions. Inter-group differences (PD vs HS) were studied using non-parametric statistics and complemented with Cohen's d effect sizes and Bayesian statistics. Correlation analyses were performed exploring biomarker dependencies and their association with bradykinesia scores. PD patients exhibited a significant decline in nigrostriatal dopaminergic activity, being post-commissural putamen (-67%) and posterolateral SNc (-11.7%) the most affected subregions within striatum and SNc respectively. Microstructural alterations (FW) were restricted to the hemisphere corresponding to the most affected side and followed similar spatial gradients as FDOPA Ki (+20% in posterior putamen and +11% in posterolateral SNc). R2* revealed no relevant significant changes. FDOPA and FW were correlated within the posterolateral SNc, and clinical severity was associated with FDOPA Ki loss. The asymmetry between striatal and SNc changes for both dopaminergic depletion and microstructural degeneration biomarkers is consistent with a neurodegenerative process that begins in the striatal terminals before progressing toward the cell bodies in the SNc.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://www.nature.com/articles/s41531-023-00586-x
http://hdl.handle.net/20.500.12020/1559
https://doi.org/10.1038/s41531-023-00586-x
url https://www.nature.com/articles/s41531-023-00586-x
http://hdl.handle.net/20.500.12020/1559
https://doi.org/10.1038/s41531-023-00586-x
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Depósito Digital e-UCJC
instname:Universidad Camilo José Cela (UCJC)
instname_str Universidad Camilo José Cela (UCJC)
reponame_str Depósito Digital e-UCJC
collection Depósito Digital e-UCJC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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