Comparison of phosphodiesterase 10A and dopamine transporter levels as markers of disease burden in early Parkinson's disease
Author(s)
Piccini, Paola
Pagano, Gennaro
Politis, Marios
Type
Journal Article
Abstract
Background
Recent work has shown loss of phosphodiesterase 10A levels in middle‐stage and advanced treated patients with PD, which was associated with motor symptom severity.
Objectives
To assess phosphodiesterase 10A levels in early PD and compare with loss of dopamine transporter as markers of disease burden.
Methods
Seventy‐eight subjects were included in this study (17 early de novo, 15 early l‐dopa–treated, 24 moderate‐advanced l‐dopa–treated patients with PD, and 22 healthy controls). All participants underwent [11C]IMA107 PET, [11C]PE2I PET, and 3‐Tesla MRI scan.
Results
Early de novo PD patients showed loss of [11C]IMA107 and of [11C]PE2I binding in caudate and putamen (P < 0.001); early l‐dopa–treated PD patients showed additional loss of [11C]IMA107 in the caudate (P < 0.001; annual decline 3.6%) and putamen (P < 0.001; annual decline 2.8%), but loss of [11C]PE2I only in the putamen (P < 0.001; annual decline 6.8%). Lower [11C]IMA107 correlated with lower [11C]PE2I in the caudate (rho = 0.51; P < 0.01) and putamen (rho = 0.53; P < 0.01). Longer disease duration correlated with lower [11C]IMA107 in the caudate (rho = –0.72; P < 0.001) and putamen (rho = –0.48; P < 0.01), and with lower [11C]PE2I only in the putamen (rho = –0.65; P < 0.001). Higher burden of motor symptoms correlated with lower [11C]IMA107 in the caudate (rho = –0.42; P < 0.05) and putamen (rho = –0.41; P < 0.05), and with lower [11C]PE2I only in the putamen (rho = –0.69; P < 0.001).
Conclusion
Our findings demonstrate loss of phosphodiesterase 10A levels very early in the course of PD and is associated with the gradual and progressive increase of motor symptoms. Phosphodiesterase 10A imaging shows similar potential with dopamine transporter imaging to follow disease progression.
Recent work has shown loss of phosphodiesterase 10A levels in middle‐stage and advanced treated patients with PD, which was associated with motor symptom severity.
Objectives
To assess phosphodiesterase 10A levels in early PD and compare with loss of dopamine transporter as markers of disease burden.
Methods
Seventy‐eight subjects were included in this study (17 early de novo, 15 early l‐dopa–treated, 24 moderate‐advanced l‐dopa–treated patients with PD, and 22 healthy controls). All participants underwent [11C]IMA107 PET, [11C]PE2I PET, and 3‐Tesla MRI scan.
Results
Early de novo PD patients showed loss of [11C]IMA107 and of [11C]PE2I binding in caudate and putamen (P < 0.001); early l‐dopa–treated PD patients showed additional loss of [11C]IMA107 in the caudate (P < 0.001; annual decline 3.6%) and putamen (P < 0.001; annual decline 2.8%), but loss of [11C]PE2I only in the putamen (P < 0.001; annual decline 6.8%). Lower [11C]IMA107 correlated with lower [11C]PE2I in the caudate (rho = 0.51; P < 0.01) and putamen (rho = 0.53; P < 0.01). Longer disease duration correlated with lower [11C]IMA107 in the caudate (rho = –0.72; P < 0.001) and putamen (rho = –0.48; P < 0.01), and with lower [11C]PE2I only in the putamen (rho = –0.65; P < 0.001). Higher burden of motor symptoms correlated with lower [11C]IMA107 in the caudate (rho = –0.42; P < 0.05) and putamen (rho = –0.41; P < 0.05), and with lower [11C]PE2I only in the putamen (rho = –0.69; P < 0.001).
Conclusion
Our findings demonstrate loss of phosphodiesterase 10A levels very early in the course of PD and is associated with the gradual and progressive increase of motor symptoms. Phosphodiesterase 10A imaging shows similar potential with dopamine transporter imaging to follow disease progression.
Date Issued
2019-10
Date Acceptance
2019-05-01
Citation
Movement Disorders, 2019, 34 (10), pp.1505-1515
ISSN
0885-3185
Publisher
Wiley
Start Page
1505
End Page
1515
Journal / Book Title
Movement Disorders
Volume
34
Issue
10
Copyright Statement
© 2019 International Parkinson and Movement Disorder Society. This is the peer reviewed version of the following article: Pagano, G. , Niccolini, F. , Wilson, H. , Yousaf, T. , Khan, N. L., Martino, D. , Plisson, C. , Gunn, R. N., Rabiner, E. A., Piccini, P. , Foltynie, T. and Politis, M. (2019), Comparison of phosphodiesterase 10A and dopamine transporter levels as markers of disease burden in early Parkinson's disease. Mov Disord. doi:10.1002/mds.27733, which has been published in final form at https://doi.org/10.1002/mds.27733. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Identifier
https://onlinelibrary.wiley.com/doi/full/10.1002/mds.27733
Subjects
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences & Neurology
PDE10A
DAT
PET
Parkinson's disease
biomarkers
IMMUNOHISTOCHEMICAL LOCALIZATION
DIAGNOSTIC-CRITERIA
METAANALYSIS
BRAIN
RAT
PROGRESSION
EXPRESSION
SEVERITY
STRIATUM
DAT
PDE10A
PET
Parkinson's disease
biomarkers
1103 Clinical Sciences
1106 Human Movement and Sports Sciences
1702 Cognitive Sciences
Neurology & Neurosurgery
Publication Status
Published
Date Publish Online
2019-06-03