Background Leucine-rich repeat kinase 2 kinase inhibitors are being
vigorously pursued as potential therapeutic options; however, there is a
critical need for sensitive and quantitative assays of leucine-rich
repeat kinase 2 function and target engagement. Objectives Our objective
was to compare collection and storage protocols for peripheral blood
mononuclear cells, and to determine the optimal conditions for
downstream analyses of leucine-rich repeat kinase 2 in PD cohorts.
Methods Here, we describe enzyme-linked immunosorbent assay-based assays
capable of detecting multiple aspects of leucine-rich repeat kinase 2
function at endogenous levels in human tissues. Results In peripheral
blood mononuclear cells from both healthy and affected carriers of the
G2019S mutation in leucine-rich repeat kinase 2, we report, for the
first time, significantly elevated in vitro kinase activity, while
detecting a significant increase in pS935/leucine-rich repeat kinase 2
in idiopathic PD patients. Conclusions Quantitative assays such as these
described here could potentially uncover specific markers of
leucine-rich repeat kinase 2 function that are predictive of disease
progression, aid in patient stratification, and be a critical component
of upcoming clinical trials. (c) 2020 International Parkinson and
Movement Disorder Societ
