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Neurodegenerative Dis 2008;5:222–224

Leucine-Rich Repeat Kinase 2 Colocalizes with α-Synuclein in Parkinson’s Disease, but Not Tau-Containing Deposits in Tauopathies

Perry G.a, b · Zhu X.a · Babar A.K.a · Siedlak S.L.a · Yang Q.a · Ito G.c · Iwatsubo T.c · Smith M.A.a · Chen S.G.a
aDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, and bCollege of Sciences, The University of Texas at San Antonio, San Antonio, Tex., USA; cDepartment of Neuropathology and Neuroscience, University of Tokyo, Tokyo, Japan
email Corresponding Author

 goto top of outline Key Words

  • Lewy bodies
  • Leucine-rich repeat kinase 2
  • Parkinson’s disease
  • Synuclein

 goto top of outline Abstract

Background: Mutations in leucine-rich repeat kinase 2 (LRRK2) are thus far the most frequent genetic cause associated with autosomal dominant and idiopathic Parkinson’s disease. Objective:To examine whether LRRK2 is directly associated with the pathological structures of Parkinson’s disease, dementia with Lewy bodies, and other related disorders using highly specific antibodies to LRRK2. Results:LRRK2 antibodies strongly labeled brainstem and cortical Lewy bodies, the pathological hallmarks of Parkinson’s disease and dementia with Lewy bodies, respectively. We found that 20–100% (mean 60%) of α-synuclein-positive Lewy bodies contained LRRK2. While antibodies raised against various regions of LRRK2 were previously shown to label recombinant LRRK2 on Western blots, only antibodies raised against the N- and C-termini, but not the regions containing folded protein domains of LRRK2, immunolabeled Lewy bodies. In Alzheimer’s disease, Hirano bodies were found to contain LRRK2 and the neurofibrillary tangles in progressive supranuclear palsy remained unlabeled. Conclusions: Information on the cellular localization of LRRK2 under normal and pathological conditions will deepen our understanding of its functions and molecular pathways relevant to the progression of Parkinson’s disease and related disorders.

Copyright © 2008 S. Karger AG, Basel

 goto top of outline References
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    External Resources

  4. Zhu X, Siedlak SL, Smith MA, Perry G, Chen SG: LRRK2 protein is a component of Lewy bodies. Ann Neurol 2006;60:617–618; author reply 618–619.
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 goto top of outline Author Contacts

George Perry, PhD
College of Sciences, University of Texas at San Antonio
One USTA Circle
San Antonio, TX 78249 (USA)
Tel. +1 210 458 4450, Fax +1 210 458 4445, E-Mail

 goto top of outline Article Information

Published online: March 6, 2008
Number of Print Pages : 3
Number of Figures : 1, Number of Tables : 0, Number of References : 10

 goto top of outline Publication Details

Neurodegenerative Diseases

Vol. 5, No. 3-4, Year 2008 (Cover Date: March 2008)

Journal Editor: Nitsch R.M. (Zürich), Hock C. (Zürich)
ISSN: 1660–2854 (Print), eISSN: 1660–2862 (Online)

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