• Kathrin Brockmann, Claudia Schulte, Christian Deuschle, Ann-Kathrin Hauser, Tanja Heger, Thomas Gasser, Walter Maetzler, and Daniela Berg.
• Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. Electronic address: Kathrin.Brockmann@uni-tuebingen.de.
• Parkinsonism Relat. Disord. 2015 Dec 1; 21 (12): 1427-34.

BackgroundParkinson's disease (PD) patients show a large phenotypic variability probably reflecting inter-individual pathologic heterogeneity. Next to typical Lewy-body pathology, β-amyloid (Aβ) and tau pathology have been found at autopsy and several studies have reported altered CSF levels of Aβ1-42, total-Tau (t-Tau) and phosphorylated-Tau (p-Tau).ObjectivesTo evaluate whether CSF levels of neurodegenerative markers are influenced by genetics and whether specific subgroups of PD are more prone to a concomitant pathology possibly reflecting aspects of disease progression.MethodsIn an explorative study we assessed CSF profiles of Aβ1-42, t-Tau, and p-Tau longitudinally in PD patients carrying LRRK2 (n = 5) or GBA mutations (n = 12), sporadic PD patients (n = 30) and healthy controls (n = 16).ResultsCompared to healthy controls, all three PD cohorts showed lower levels of Aβ1-42. Moreover, sporadic PD and GBA-PD patients presented with lower levels of t-Tau and p-Tau whereas this phenomenon was not seen in LRRK2-PD patients. Regression analyses revealed an association between higher levels of Baseline p-Tau with more accelerated cognitive deterioration over time in LRRK2-PD and GBA-PD patients, but not in sporadic PD.ConclusionPD patients present with disease-specific CSF profiles of Aβ1-42, t-Tau and p-Tau arguing in favor of an involvement of these proteins in PD pathogenesis in both sporadic and genetic forms. Moreover, we found first hints for differences in these CSF profiles between genetically determined PD cohorts but that CSF constellations which tend to predict aspects of disease progression such as cognitive decline seem similar across subgroups of PD.Copyright © 2015 Elsevier Ltd. All rights reserved.

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