Inflammatory profile in LRRK2-associated prodromal and clinical PD

Brockmann, Kathrin; Apel, Anja; Schulte, Claudia; Schneiderhan-Marra, Nicole; Pont-Sunyer, Claustre; Vilas, Dolores; Ruiz-Martinez, Javier; Langkamp, Markus; Corvol, Jean-Christophe; Cormier, Florence; Knorpp, Thomas; Joos, Thomas O.; Gasser, Thomas; Schüle, Birgitt; Aasly, Jan O.; Foroud, Tatiana; Marti-Masso, Jose Felix; Brice, Alexis; Tolosa, Eduardo; Marras, Connie; Berg, Daniela; Maetzler, Walter ORCID

BACKGROUND There is evidence for a relevant role of inflammation in the pathogenesis of Parkinson's disease (PD). Mutations in the LRRK2 gene represent the most frequent genetic cause for autosomal dominant PD. LRRK2 is highly expressed in macrophages and microglia suggesting an involvement in inflammatory pathways. The objectives are to test (1) whether idiopathic PD and LRRK2-associated PD share common inflammatory pathways or present distinct profiles and (2) whether non-manifesting LRRK2 mutation carriers present with similar aspects of inflammatory profiles as seen in PD-affected patients. METHODS We assessed serum profiles of 23 immune-associated markers and the brain-derived neurotrophic factor in 534 individuals from the MJFF LRRK2 consortium. RESULTS A large proportion of inflammatory markers were gender-dependent. Both PD-affected cohorts showed increased levels of the pro-inflammatory marker fatty-acid-binding protein. Additionally, idiopathic PD but not LRRK2-associated PD patients showed increased levels of the pro-inflammatory marker interleukin-12-p40 as well as the anti-inflammatory species interleukin-10, brain-derived neurotrophic factor, and stem cell factor. Non-manifesting LRRK2 mutation carriers including those with prodromal characteristics of PD presented with control-like inflammatory profiles. CONCLUSIONS Concomitant inflammation seems to be associated with idiopathic and LRRK2-associated PD. Identifying PD patients in whom inflammatory processes play a major role in their pathophysiology might offer a new therapeutic window at least for a subgroup of patients. Since non-manifesting LRRK2 mutation carriers with symptoms of the prodromal phase of PD did not show inflammatory profiles, activation of the immune system seems not an early event in the disease cascade.

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Brockmann, Kathrin / Apel, Anja / Schulte, Claudia / et al: Inflammatory profile in LRRK2-associated prodromal and clinical PD. 2016.

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