Skip Navigation



Brain Advance Access published online on August 4, 2005
Brain, doi:10.1093/brain/awh607
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
128/12/2777    most recent
awh607v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Adams, J. R.
Right arrow Articles by Stoessl, A. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Adams, J. R.
Right arrow Articles by Stoessl, A. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received February 10, 2005
Revised May 30, 2005
Accepted July 4, 2005

Article

PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and evidence for presymptomatic compensation

John R. Adams 1, Hinke van Netten 1, Michael Schulzer 1, Edwin Mak 1, Jessamyn Mckenzie 1, Audrey Strongosky 2, Vesna Sossi 3, Thomas J. Ruth 4, Chong S. Lee 1, Matthew Farrer 2, Thomas Gasser 5, Ryan J. Uitti 2, Donald B. Calne 1, Zbigniew K. Wszolek 2 *, and A. Jon Stoessl 1* *

1 Pacific Parkinson's Research Centre, University of British Columbia
2 Mayo Clinic, Jacksonville, FL, USA
3 Department of Physics and Astronomy, University of British Columbia
4 TRIUMF, Vancouver, BC, Canada
5 Department of Neurodegenerative disorders, Hertie Institute for Clinical Brain Research, Center of Neurology, University of Tubingen, Tubingen, Germany

* To whom correspondence should be addressed.
A. Jon Stoessl, E-mail: jstoessl{at}interchange.ubc.ca


  Abstract

Parkinson's disease may arise from multiple aetiologies, including genetic mutations that are for the most part uncommon. We describe here the positron emission tomography (PET) findings in clinically affected and asymptomatic, high-risk members of two autosomal dominantly inherited Parkinson's disease kindreds with recently described mutations at the PARK8 locus, in a novel gene encoding a leucine-rich repeat kinase (LRRK2). Affected family members have L-dopa-responsive parkinsonism with loss of dopaminergic nigral neurons and pleomorphic subcellular pathology. Fifteen family members underwent PET using: 18F-6-fluoro-L-dopa (18F-dopa) to assess dopamine (DA) synthesis and storage, 11C-(±){alpha}-dihydrotetrabenazine (11C-DTBZ) for the vesicular monoamine transporter, and 11C-d-threo-methylphenidate (11C-MP) for the membrane dopamine transporter (DAT). Measurements were compared with normal (n = 33) and sporadic Parkinson's disease (sPD) (n = 67) control groups. Four clinically affected members had findings similar to sPD, with impaired presynaptic DA function affecting the putamen more than the caudate. In two affected members, D2 dopamine receptor binding was intact. Two asymptomatic mutation carriers had abnormal DAT binding with another two developing such abnormalities over 4 years of follow-up. In these individuals, 18F-dopa uptake remained normal, although two of them also displayed abnormal 11C-DTBZ binding. Our study demonstrates that the in vivo neurochemical phenotype of LRRK2 mutations is indistinguishable from that of sPD, despite the pathological heterogeneity of the condition. Furthermore, we suggest that compensatory changes including downregulation of the DAT and upregulation of decarboxylase activity may delay the onset of parkinsonian symptoms.

Keywords: genetics; Parkinson's disease; pathophysiology; positron emission tomography.
*These authors contributed equally to this work
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 NeurologyHome page
A. R. Troiano, R. de la Fuente-Fernandez, V. Sossi, M. Schulzer, E. Mak, T. J. Ruth, and A. J. Stoessl
PET demonstrates reduced dopamine transporter expression in PD with dyskinesias
Neurology, April 7, 2009; 72(14): 1211 - 1216.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
K. Marek and D. Jennings
Can we image premotor Parkinson disease?
Neurology, February 17, 2009; 72(7_Supplement_2): S21 - S26.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
R. Nandhagopal, E. Mak, M. Schulzer, J. McKenzie, S. McCormick, V. Sossi, T. J. Ruth, A. Strongosky, M. J. Farrer, Z. K. Wszolek, et al.
Progression of dopaminergic dysfunction in a LRRK2 kindred: A multitracer PET study
Neurology, November 25, 2008; 71(22): 1790 - 1795.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
R. Nandhagopal, M. J. McKeown, and A. J. Stoessl
Invited Article: Functional imaging in Parkinson disease
Neurology, April 15, 2008; 70(16_Part_2): 1478 - 1488.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
T. -B. Ahn, S. Y. Kim, J. Y. Kim, S. -S. Park, D. S. Lee, H. J.. Min, Y. K. Kim, S. E. Kim, J. -M. Kim, H. -J. Kim, et al.
{alpha}-Synuclein gene duplication is present in sporadic Parkinson disease
Neurology, January 1, 2008; 70(1): 43 - 49.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
C. Klein and M. G. Schlossmacher
Parkinson disease, 10 years after its genetic revolution: Multiple clues to a complex disorder
Neurology, November 27, 2007; 69(22): 2093 - 2104.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
W. C. Nichols, V. E. Elsaesser, N. Pankratz, M. W. Pauciulo, D. K. Marek, C. A. Halter, A. Rudolph, C. W. Shults, T. Foroud, and For the Parkinson Study Group PROGENI Investigato
LRRK2 mutation analysis in Parkinson disease families with evidence of linkage to PARK8
Neurology, October 30, 2007; 69(18): 1737 - 1744.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
A. Kas, P. Payoux, M.-O. Habert, Z. Malek, Y. Cointepas, G. El Fakhri, P. Chaumet-Riffaud, E. Itti, and P. Remy
Validation of a Standardized Normalization Template for Statistical Parametric Mapping Analysis of 123I-FP-CIT Images
J. Nucl. Med., September 1, 2007; 48(9): 1459 - 1467.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
F. Binkofski, K. Reetz, C. Gaser, R. Hilker, J. Hagenah, K. Hedrich, T. van Eimeren, A. Thiel, C. Buchel, P. P. Pramstaller, et al.
Morphometric fingerprint of asymptomatic Parkin and PINK1 mutation carriers in the basal ganglia
Neurology, August 28, 2007; 69(9): 842 - 850.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
C. Iaccarino, C. Crosio, C. Vitale, G. Sanna, M. T. Carri, and P. Barone
Apoptotic mechanisms in mutant LRRK2-mediated cell death
Hum. Mol. Genet., June 1, 2007; 16(11): 1319 - 1326.
[Abstract] [Full Text] [PDF]

Home page
 Arch NeurolHome page
A. H. V. Schapira
The Importance of LRRK2 Mutations in Parkinson Disease.
Arch Neurol, September 1, 2006; 63(9): 1225 - 1228.
[Full Text] [PDF]

Home page
 NeurologyHome page
A. H.V. Schapira
Etiology of Parkinson's disease
Neurology, May 23, 2006; 66(10_suppl_4): S10 - S23.
[Abstract] [Full Text]

Home page
 BrainHome page
A. Brice
Genetics of Parkinson's disease: LRRK2 on the rise
Brain, December 1, 2005; 128(12): 2760 - 2762.
[Full Text] [PDF]

Home page
 BrainHome page
N. L. Khan, S. Jain, J. M. Lynch, N. Pavese, P. Abou-Sleiman, J. L. Holton, D. G. Healy, W. P. Gilks, M. G. Sweeney, M. Ganguly, et al.
Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data
Brain, December 1, 2005; 128(12): 2786 - 2796.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. B. West, D. J. Moore, S. Biskup, A. Bugayenko, W. W. Smith, C. A. Ross, V. L. Dawson, and T. M. Dawson
From The Cover: Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity
PNAS, November 15, 2005; 102(46): 16842 - 16847.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.