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Localization of Parkinson's disease-associated LRRK2 in normal and pathological human brain.

Publication ,  Journal Article
Higashi, S; Biskup, S; West, AB; Trinkaus, D; Dawson, VL; Faull, RLM; Waldvogel, HJ; Arai, H; Dawson, TM; Moore, DJ; Emson, PC
Published in: Brain Res
June 25, 2007

Mutations in the LRRK2 gene cause autosomal dominant, late-onset parkinsonism, which presents with pleomorphic pathology including alpha-synucleopathy. To promote our understanding of the biological role of LRRK2 in the brain we examined the distribution of LRRK2 mRNA and protein in postmortem human brain tissue from normal and neuropathological subjects. In situ hybridization and immunohistochemical analysis demonstrate the expression and localization of LRRK2 to various neuronal populations in brain regions implicated in Parkinson's disease (PD) including the cerebral cortex, caudate-putamen and substantia nigra pars compacta. Immunofluorescent double labeling studies additionally reveal the prominent localization of LRRK2 to cholinergic-, calretinin- and GABA(B) receptor 1-positive, dopamine-innervated, neuronal subtypes in the caudate-putamen. The distribution of LRRK2 in brain tissue from sporadic PD and dementia with Lewy bodies (DLB) subjects was also examined. In PD brains, LRRK2 immunoreactivity localized to nigral neuronal processes is dramatically reduced which reflects the disease-associated loss of dopaminergic neurons in this region. However, surviving nigral neurons occasionally exhibit LRRK2 immunostaining of the halo structure of Lewy bodies. Moreover, LRRK2 immunoreactivity is not associated with Lewy neurites or with cortical Lewy bodies in sporadic PD and DLB brains. These observations indicate that LRRK2 is not a primary component of Lewy bodies and does not co-localize with mature fibrillar alpha-synuclein to a significant extent. The localization of LRRK2 to key neuronal populations throughout the nigrostriatal dopaminergic pathway is consistent with the involvement of LRRK2 in the molecular pathogenesis of familial and sporadic parkinsonism.

Duke Scholars

Published In

Brain Res

DOI

ISSN

0006-8993

Publication Date

June 25, 2007

Volume

1155

Start / End Page

208 / 219

Location

Netherlands

Related Subject Headings

  • Reference Values
  • Putamen
  • Protein Serine-Threonine Kinases
  • Parkinsonian Disorders
  • Neurons
  • Neurology & Neurosurgery
  • Mutation
  • Lewy Bodies
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • In Situ Hybridization
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Higashi, S., Biskup, S., West, A. B., Trinkaus, D., Dawson, V. L., Faull, R. L. M., … Emson, P. C. (2007). Localization of Parkinson's disease-associated LRRK2 in normal and pathological human brain. Brain Res, 1155, 208–219. https://doi.org/10.1016/j.brainres.2007.04.034
Higashi, Shinji, Saskia Biskup, Andrew B. West, Daniel Trinkaus, Valina L. Dawson, Richard L. M. Faull, Henry J. Waldvogel, et al. “Localization of Parkinson's disease-associated LRRK2 in normal and pathological human brain.Brain Res 1155 (June 25, 2007): 208–19. https://doi.org/10.1016/j.brainres.2007.04.034.
Higashi S, Biskup S, West AB, Trinkaus D, Dawson VL, Faull RLM, et al. Localization of Parkinson's disease-associated LRRK2 in normal and pathological human brain. Brain Res. 2007 Jun 25;1155:208–19.
Higashi, Shinji, et al. “Localization of Parkinson's disease-associated LRRK2 in normal and pathological human brain.Brain Res, vol. 1155, June 2007, pp. 208–19. Pubmed, doi:10.1016/j.brainres.2007.04.034.
Higashi S, Biskup S, West AB, Trinkaus D, Dawson VL, Faull RLM, Waldvogel HJ, Arai H, Dawson TM, Moore DJ, Emson PC. Localization of Parkinson's disease-associated LRRK2 in normal and pathological human brain. Brain Res. 2007 Jun 25;1155:208–219.
Journal cover image

Published In

Brain Res

DOI

ISSN

0006-8993

Publication Date

June 25, 2007

Volume

1155

Start / End Page

208 / 219

Location

Netherlands

Related Subject Headings

  • Reference Values
  • Putamen
  • Protein Serine-Threonine Kinases
  • Parkinsonian Disorders
  • Neurons
  • Neurology & Neurosurgery
  • Mutation
  • Lewy Bodies
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • In Situ Hybridization