Imaging dopamine function and microglia in asymptomatic LRRK2 mutation carriers

Morten Gersel Stokholm; Alicia Garrido; Eduardo Tolosa; Mónica Serradell; Alex Iranzo; Karen Østergaard; Per Borghammer; Arne Møller; Peter Parbo; Kristian Stær; David J. Brooks; Maria José Martí; Nicola Pavese

doi:10.1007/s00415-020-09830-3

Imaging dopamine function and microglia in asymptomatic LRRK2 mutation carriers

Morten Gersel Stokholm, Alicia Garrido, Eduardo Tolosa, Mónica Serradell, Alex Iranzo, Karen Østergaard, Per Borghammer, Arne Møller, Peter Parbo, Kristian Stær, David J. Brooks, Maria José Martí, Nicola Pavese^*

^*Kontaktforfatter

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Abstract

Neuroinflammation (microglial activation) and subclinical nigrostriatal dysfunction have been reported in subjects at risk of Parkinsonism. Eight non-manifesting carriers (NMCs) of LRRK2 G2019S mutation had ¹¹C-PK11195 and ¹⁸F-DOPA PET to assess microglial activation and striatal dopamine system integrity, respectively. Comparisons were made with healthy controls. Five LRRK2-NMCs had subclinical reductions of putaminal ¹⁸F-DOPA uptake. Three of them had significantly raised nigral ¹¹C-PK11195 binding bilaterally. These findings indicate that nigrostriatal dysfunction and neuroinflammation occur in LRRK2-NMCs. Studies in larger cohorts with appropriate follow-up are needed to elucidate the significance of neuroinflammation in the premotor phase of LRRK2-PD.

Originalsprog	Engelsk
Tidsskrift	Journal of Neurology
Vol/bind	267
Udgave nummer	8
Sider (fra-til)	2296-2300
ISSN	0340-5354
DOI	https://doi.org/10.1007/s00415-020-09830-3
Status	Udgivet - 1. aug. 2020
Udgivet eksternt	Ja

Bibliografisk note

Funding Information:
We thank all study participants and biomedical laboratory scientists and radiochemists (Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Denmark) for technical assistance, and our study coordinator Anne Sofie Møller Andersen (Danish Neuroscience Centre, Aarhus University, Denmark).

Funding Information:
ET reports grants from the MJFox Foundation and the Instituto de Salud Carlos III. KØ reports grants from The Danish Parkinson Association, The Danish Council for Independent Research, and Lundbeck Foundation, during the conduct of the study and personal fees from Medtronic Inc., UCB, Fertin Pharma, and AbbVie outside the submitted work. DJB reports grants from The Danish Council for Independent Research, Lundbeck Foundation, The Danish Parkinson Association, European Union FP7 programme, and Alzheimer Research UK and personal fees from GE Healthcare and Plexxikon outside the submitted work. NP reports grants from The Danish Council for Independent Research during the conduct of the study. The other authors declare no competing interests.

Publisher Copyright:
© 2020, The Author(s).

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Citationsformater

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abstract = "Neuroinflammation (microglial activation) and subclinical nigrostriatal dysfunction have been reported in subjects at risk of Parkinsonism. Eight non-manifesting carriers (NMCs) of LRRK2 G2019S mutation had 11C-PK11195 and 18F-DOPA PET to assess microglial activation and striatal dopamine system integrity, respectively. Comparisons were made with healthy controls. Five LRRK2-NMCs had subclinical reductions of putaminal 18F-DOPA uptake. Three of them had significantly raised nigral 11C-PK11195 binding bilaterally. These findings indicate that nigrostriatal dysfunction and neuroinflammation occur in LRRK2-NMCs. Studies in larger cohorts with appropriate follow-up are needed to elucidate the significance of neuroinflammation in the premotor phase of LRRK2-PD.",

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T1 - Imaging dopamine function and microglia in asymptomatic LRRK2 mutation carriers

AU - Gersel Stokholm, Morten

AU - Garrido, Alicia

AU - Tolosa, Eduardo

AU - Serradell, Mónica

AU - Iranzo, Alex

AU - Østergaard, Karen

AU - Borghammer, Per

AU - Møller, Arne

AU - Parbo, Peter

AU - Stær, Kristian

AU - Brooks, David J.

AU - Martí, Maria José

AU - Pavese, Nicola

PY - 2020/8/1

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N2 - Neuroinflammation (microglial activation) and subclinical nigrostriatal dysfunction have been reported in subjects at risk of Parkinsonism. Eight non-manifesting carriers (NMCs) of LRRK2 G2019S mutation had 11C-PK11195 and 18F-DOPA PET to assess microglial activation and striatal dopamine system integrity, respectively. Comparisons were made with healthy controls. Five LRRK2-NMCs had subclinical reductions of putaminal 18F-DOPA uptake. Three of them had significantly raised nigral 11C-PK11195 binding bilaterally. These findings indicate that nigrostriatal dysfunction and neuroinflammation occur in LRRK2-NMCs. Studies in larger cohorts with appropriate follow-up are needed to elucidate the significance of neuroinflammation in the premotor phase of LRRK2-PD.

AB - Neuroinflammation (microglial activation) and subclinical nigrostriatal dysfunction have been reported in subjects at risk of Parkinsonism. Eight non-manifesting carriers (NMCs) of LRRK2 G2019S mutation had 11C-PK11195 and 18F-DOPA PET to assess microglial activation and striatal dopamine system integrity, respectively. Comparisons were made with healthy controls. Five LRRK2-NMCs had subclinical reductions of putaminal 18F-DOPA uptake. Three of them had significantly raised nigral 11C-PK11195 binding bilaterally. These findings indicate that nigrostriatal dysfunction and neuroinflammation occur in LRRK2-NMCs. Studies in larger cohorts with appropriate follow-up are needed to elucidate the significance of neuroinflammation in the premotor phase of LRRK2-PD.

KW - Clinical neurology

KW - Genetics

KW - Movement disorders

KW - Parkinson’s disease

KW - PET

U2 - 10.1007/s00415-020-09830-3

DO - 10.1007/s00415-020-09830-3

M3 - Journal article

C2 - 32318850

AN - SCOPUS:85083709219

SN - 0340-5354

VL - 267

SP - 2296

EP - 2300

JO - Journal of Neurology

JF - Journal of Neurology

IS - 8

ER -

Imaging dopamine function and microglia in asymptomatic LRRK2 mutation carriers

Abstract

Bibliografisk note

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