Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease.
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.
Fraser, KB; Rawlins, AB; Clark, RG; Alcalay, RN; Standaert, DG; Liu, N; Parkinson's Disease Biomarker Program Consortium, ; West, AB
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