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Open Access 01-12-2006 | Research article

LRRK2 in Parkinson's disease and dementia with Lewy bodies

Authors: Xiongwei Zhu, Asim Babar, Sandra L Siedlak, Qiwei Yang, Genta Ito, Takeshi Iwatsubo, Mark A Smith, George Perry, Shu G Chen

Published in: Molecular Neurodegeneration | Issue 1/2006

Abstract

Background

Mutations in LRRK2 encoding leucine-rich repeat kinase 2 are thus far the most frequent genetic cause associated with autosomal dominant and idiopathic Parkinson's disease (PD). To examine whether LRRK2 is directly associated with neuropathology of PD and other related disorders, we analyzed LRRK2 in brains of patients affected by PD and dementia with Lewy bodies (DLB) using highly specific antibodies to LRRK2.

Results

We demonstrated that anti-LRRK2 antibodies strongly labelled brainstem and cortical Lewy bodies, the pathological hallmarks of PD and DLB, respectively. In addition, anti-LRRK2 also labelled brain vasculature, axons, and neuronal cell bodies. Interestingly, the immunocytochemical profile of LRRK2 varied with different antibodies depending upon specific antigenic sites along the LRRK2 protein. All anti-LRRK2 antibodies tested that were raised against various regions of LRRK2, were found to be immunoreactive to recombinant LRRK2 on Western blots. However, only the antibodies raised against the N-terminal and C-terminal regions of LRRK2, but not the regions containing folded protein domains, were positive in immunolabeling of Lewy bodies, suggesting a differential exposure of specific antigenic sites of LRRK2 on tissue sections.

Conclusion

We conclude that LRRK2 is a component of Lewy bodies in both PD and DLB, and therefore plays an important role in the Lewy body formation and disease pathogenesis. 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 PD and related disorders.

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Title: LRRK2 in Parkinson's disease and dementia with Lewy bodies
Authors: Xiongwei Zhu
Asim Babar
Sandra L Siedlak
Qiwei Yang
Genta Ito
Takeshi Iwatsubo
Mark A Smith
George Perry
Shu G Chen
Publication date: 01-12-2006
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2006
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/1750-1326-1-17

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

LRRK2 in Parkinson's disease and dementia with Lewy bodies

Abstract

Background

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Results

Conclusion

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