Alterations in the LRRK2-Rab pathway in urinary extracellular vesicles as Parkinson's disease and pharmacodynamic biomarkers.

Expression or phosphorylation levels of leucine-rich repeat kinase 2 (LRRK2) and its Rab substrates have strong potential as disease or pharmacodynamic biomarkers. The main objective of this study is therefore to assess the LRRK2-Rab pathway for use as biomarkers in human, non-human primate (NHP) and rat urine. With urine collected from human subjects and animals, we applied an ultracentrifugation based fractionation protocol to isolate small urinary extracellular vesicles (uEVs).

Centrosomal cohesion deficits as cellular biomarker in lymphoblastoid cell lines from LRRK2 Parkinson's disease patients.

Leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for the treatment of Parkinson's disease (PD), and orally bioavailable, brain penetrant and highly potent LRRK2 kinase inhibitors are in early stages of clinical testing. Detection of LRRK2 phosphorylation, as well as phosphorylation of Rab10, a LRRK2 kinase substrate, have been proposed as target engagement biomarkers for LRRK2 inhibitor clinical trials. However, these readouts do not seem able to stratify patients based on enhanced LRRK2 kinase activity.

Freezing/festination during motor tasks in early-stage Parkinson's disease: A prospective study.

Background: Parkinsonian patients have a tendency to speed up during repetitive motor tasks (festination) and to experience sudden motor blocks (freezing). In this article, we prospectively studied the appearance and progression of these phenomena in 30 early-stage PD patients.

Methods: A total of 30 controls and early-stage PD patients were assessed in the "off-drug" condition at baseline and 2 years later.

Auditory cueing of gait initiation in Parkinson's disease patients with freezing of gait.

Objective: Impaired gait initiation (GI) in patients with advanced Parkinson's disease (PD) is a typical functional sign of akinesia. Failure to initiate the first step is frequently presented by patients with freezing of gait (FOG) and is often considered a sub-type of freezing. The literature on the effects of cueing of GI preparation and execution remains controversial.

Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporadic forms of Parkinson's disease.

The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is a common genetic cause of Parkinson's disease (PD). Although patients with sporadic PD and individuals with LRRK2-linked PD display the classical PD phenotype, it is not known whether or not the same biological pathways are deregulated in each context. By using transcriptome profiling, we investigated the deregulation of various biological pathways in a total of 47 peripheral blood mononuclear cell (PBMC) samples from patients with sporadic PD, patients heterozygous for the LRRK2 G2019S mutation compared to healthy controls.

Are gait initiation parameters early markers of Huntington's disease in pre-manifest mutation carriers?

Huntington's disease (HD) pre-manifest mutation carriers (PMCs) present early-onset gait disturbances. Gait initiation encompasses the preparation and execution of the first step. By using paradigms with and without external cues, a gait initiation analysis can highlight the interaction between motor and cognitive aspects of movement preparation and execution.

Kinematic angular parameters in PD: reliability of joint angle curves and comparison with healthy subjects.

Background: Most previous biomechanical studies of Parkinson's disease (PD) have been restricted to the description of spatiotemporal parameters and certain peak values for angular parameters. The reliability of joint angle curves and comparisons with control data are of major interest in PD, since variability in gait cycle timing is a feature of this pathology.

Methods: We used a video motion analysis system to record kinematic, spatiotemporal and angular parameters in 32 'off-drug' PD patients.

Effect of age on anticipatory postural adjustments in unilateral arm movement.

Aging is frequently accompanied by a deterioration in postural control. Accordingly, the elderly adopt postural strategies in order to maintain balance. The purpose of this study was to compare anticipatory postural adjustments in (healthy) 10 young and 10 elderly subjects using electromyography (EMG) and biomechanical parameters.

Vertical torque allows recording of anticipatory postural adjustments associated with slow, arm-raising movements.

Background: When performed in the upright position, voluntary arm-raising movements perturb balance. The maintenance of equilibrium requires postural adjustments, some of which can be anticipatory. It is usually suggested that the role of anticipatory postural adjustments is to stabilise the whole body centre of mass.

[Anticipatory postural adjustments associated with arm flexion: interest of vertical torque].

Objective: To find a biomechanical parameter able to characterize postural adjustments in different movement conditions.

Methods: The arm-raising movement performed during the upright human position imposes a vertical torque (Tz) that can be measured by a force plate-form. This torque was studied in ten healthy young subjects with opto electronic system Vicon 370.