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Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease.

Publication ,  Journal Article
Fraser, KB; Rawlins, AB; Clark, RG; Alcalay, RN; Standaert, DG; Liu, N; Parkinson's Disease Biomarker Program Consortium; West, AB
Published in: Mov Disord
October 2016

BACKGROUND: Mutations in Leucine-rich repeat kinase 2 (LRRK2) enhance levels of the autophosphorylated LRRK2 protein and are the most common known cause of inherited Parkinson's disease (PD). LRRK2 has been further implicated in susceptibility to idiopathic PD in genetic association studies. OBJECTIVE: The objective of this study was to compare autophosphorylated Ser(P)-1292 LRRK2 levels from biobanked urine samples with clinical data in PD patients and controls. METHODS: Ser(P)-1292 LRRK2 levels were measured from urine exosome fractions from 79 PD patients and 79 neurologically healthy controls enrolled in the Parkinson Disease Biomarker Program at the University of Alabama at Birmingham. RESULTS: Ser(P)-1292 LRRK2 levels were higher in men than women (P < .0001) and elevated in PD patients when compared with controls (P = .0014). Ser(P)-1292 LRRK2 levels were higher in PD cases with worse cognition and correlated with poor performance in MoCA (r = -0.2679 [-0.4628 to -0.0482]), MDS-UPDRS subscales 1 and 2 (r = 0.2239 [0.0014-0.4252], 0.3404 [0.1276-0.5233], respectively), Epworth Sleepiness Scale (r = 0.3215 [0.1066-0.5077]), and Modified Schwab and England Activities of Daily Living Scales (r = -0.4455 [-0.6078 to -0.2475]). Ser(P)-1292 LRRK2 levels predicted those with worse cognitive impairment in PD patients with some success (c = 0.73). CONCLUSIONS: Urinary exosome Ser(P)-1292 LRRK2 levels are elevated in idiopathic PD and correlated with the severity of cognitive impairment and difficultly in accomplishing activities of daily living. These results implicate biochemical changes in LRRK2 in idiopathic PD. © 2016 International Parkinson and Movement Disorder Society.

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Published In

Mov Disord

DOI

EISSN

1531-8257

Publication Date

October 2016

Volume

31

Issue

10

Start / End Page

1543 / 1550

Location

United States

Related Subject Headings

  • Severity of Illness Index
  • Phosphorylation
  • Parkinson Disease
  • Neurology & Neurosurgery
  • Middle Aged
  • Male
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Humans
  • Female
  • Exosomes
 

Citation

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Fraser, K. B., Rawlins, A. B., Clark, R. G., Alcalay, R. N., Standaert, D. G., Liu, N., … West, A. B. (2016). Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease. Mov Disord, 31(10), 1543–1550. https://doi.org/10.1002/mds.26686
Fraser, Kyle B., Ashlee B. Rawlins, Rachel G. Clark, Roy N. Alcalay, David G. Standaert, Nianjun Liu, Parkinson’s Disease Biomarker Program Consortium, and Andrew B. West. “Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease.Mov Disord 31, no. 10 (October 2016): 1543–50. https://doi.org/10.1002/mds.26686.
Fraser KB, Rawlins AB, Clark RG, Alcalay RN, Standaert DG, Liu N, et al. Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease. Mov Disord. 2016 Oct;31(10):1543–50.
Fraser, Kyle B., et al. “Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease.Mov Disord, vol. 31, no. 10, Oct. 2016, pp. 1543–50. Pubmed, doi:10.1002/mds.26686.
Fraser KB, Rawlins AB, Clark RG, Alcalay RN, Standaert DG, Liu N, Parkinson’s Disease Biomarker Program Consortium, West AB. Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease. Mov Disord. 2016 Oct;31(10):1543–1550.
Journal cover image

Published In

Mov Disord

DOI

EISSN

1531-8257

Publication Date

October 2016

Volume

31

Issue

10

Start / End Page

1543 / 1550

Location

United States

Related Subject Headings

  • Severity of Illness Index
  • Phosphorylation
  • Parkinson Disease
  • Neurology & Neurosurgery
  • Middle Aged
  • Male
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Humans
  • Female
  • Exosomes