Session Information
Date: Tuesday, June 21, 2016
Session Title: Genetics (PD and Non-PD)
Session Time: 12:30pm-2:00pm
Objective: To evaluate whether inflammatory processes in PD patients with mutations in the LRRK2 gene (PD-LRRK2) are associated with modification of clinical features and disease course.
Background: The presentation of PD-LRRK2 is highly variable, suggesting a strong influence of genetic or non-genetic modifying factors. In this context, inflammation is a potential candidate inducing clinical subtypes.
Methods: An extensive battery of peripheral immune-associated markers were measured in a multicenter cohort of 142 PD-LRRK2 patients from the MJFF LRRK2 consortium, stratified by the three different clinical subtypes as recently proposed for idiopathic PD (IPD): a) Diffuse/Malignant (cognitive impairment, orthostatic hypotension, REM sleep behaviour disorder), b) Intermediate and c) Mainly Pure Motor. Group comparison as well as discriminant analysis including all assessed serum markers was performed to test whether specific immune profiles could discriminate the clinical phenotypes.
Results: Patients classified as Diffuse/Malignant presented with the highest levels of the pro-inflammatory proteins Interleukin 8 (IL-8), Monocyte chemotactic protein 1 (MCP-1), and Macrophage inflammatory protein-1-beta (MIP-1-beta) paralleled by high levels of the neurotrophic protein Brain-derived neurotrophic factor (BDNF). It was also possible to distinguish the clinical subtypes based on their immune-marker profile by using discriminant analysis.
Conclusions: Inflammation seems to be associated with the presence of a specific clinical subtype in PD-LRRK2 that is characterized by a broad and more severely affected spectrum of motor and non-motor symptoms. The pro-inflammatory metabolites IL-8, MCP-1 and MIP-1-beta as well as BDNF are interesting candidates to be included in biomarker panels that aim to differentiate subtypes in PD-LRRK2 and predict progression.
To cite this abstract in AMA style:
K. Brockmann, C. Schulte, N. Schneiderhan-Marra, A. Apel, C. Pont-Sunyer, D. Vilas, J. Ruiz-Martinez, M. Langkamp, J.C. Corvol, F. Cormier, T. Knorpp, T.O. Joos, A. Bernhard, T. Gasser, C. Marras, B. Schüle, J.O. Aasly, T. Foroud, J.F. Marti-Masso, A. Brice, E. Tolosa, D. Berg, W. Maetzler. Inflammatory profile discriminates clinical subtypes in LRRK2-associated PD [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/inflammatory-profile-discriminates-clinical-subtypes-in-lrrk2-associated-pd/. Accessed June 14, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/inflammatory-profile-discriminates-clinical-subtypes-in-lrrk2-associated-pd/