LRRK2 levels and phosphorylation in Parkinson's disease brain and cases with restricted Lewy bodies
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Updated: Mar 11, 2026
Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate
Published on: September 18, 2013
Nicolas Dzamko1,2, Amanda M Gysbers2, Rina Bandopadhyay3
1School of Medical Sciences, University of New South Wales, Kensington, Australia.
Background:
Leucine rich repeat kinase 2 (LRRK2) is a promising target for the treatment of Parkinson's disease; however, little is known about the expression of LRRK2 in human brain and if/how LRRK2 protein levels are altered in Parkinson's disease.
Objectives:
We measured the protein levels of LRRK2 as well as its phosphorylation on serines 910, 935, and 973 in the postmortem brain tissue of Parkinson's disease patients and aged controls with and without Lewy bodies.
Methods:
LRRK2 and its phosphorylation were measured by immunoblot in brain regions differentially affected in Parkinson's disease (n = 30) as well as subjects with Lewy bodies restricted to the periphery and lower brain stem (n = 25) and matched controls without pathology (n = 25).
Results:
LRRK2 levels were increased in cases with restricted Lewy bodies, with a 30% increase measured in the substantia nigra. In clinical Parkinson's disease, levels of LRRK2 negatively correlated to disease duration and were comparable with controls. LRRK2 phosphorylation, however, particularly at serine 935, was reduced with clinical Parkinson's disease with a 36% reduction measured in the substantia nigra.
Conclusions:
Our data show that LRRK2 phosphorylation is reduced with clinical PD, whereas LRRK2 expression is increased in early potential prodromal stages. These results contribute to a better understanding of the role of LRRK2 in idiopathic Parkinson's disease and may aid efforts aimed at therapeutically targeting the LRRK2 protein. © 2016 International Parkinson and Movement Disorder Society.
Insights
Leucine rich repeat kinase 2 (LRRK2) protein levels increase in early Parkinson's disease stages, while its phosphorylation decreases in clinical Parkinson's disease. These findings offer insights into LRRK2's role in Parkinson's disease pathogenesis.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- Leucine rich repeat kinase 2 (LRRK2) is a key target for Parkinson's disease (PD) therapies.
- Understanding LRRK2 expression and alterations in the human brain is crucial for PD treatment development.
Purpose of the Study:
- To investigate LRRK2 protein levels and phosphorylation in postmortem brain tissue from Parkinson's disease patients and controls.
- To determine how LRRK2 expression and phosphorylation vary in different brain regions affected by Parkinson's disease.
Main Methods:
- Immunoblot analysis was used to measure LRRK2 protein and its phosphorylation at serines 910, 935, and 973.
- Brain tissue from Parkinson's disease patients (n=30), individuals with Lewy bodies (n=25), and controls (n=25) was analyzed.
Main Results:
- LRRK2 levels were elevated by 30% in the substantia nigra of individuals with restricted Lewy bodies.
- In clinical Parkinson's disease, LRRK2 levels correlated inversely with disease duration and were similar to controls.
- LRRK2 phosphorylation, particularly at serine 935, was reduced by 36% in the substantia nigra of Parkinson's disease patients.
Conclusions:
- LRRK2 phosphorylation is reduced in clinical Parkinson's disease.
- LRRK2 expression increases in early, potentially prodromal stages of Parkinson's disease.
- These findings enhance understanding of LRRK2's role in idiopathic Parkinson's disease and inform therapeutic strategies targeting LRRK2.
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