Journal
PARKINSONISM & RELATED DISORDERS
Volume 21, Issue 12, Pages 1427-1434Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.parkreldis.2015.10.008
Keywords
Parkinson; CSF; Tau; Abeta; LRRK2; GBA
Categories
Funding
- University of Tuebingen (TUEFF)
- German Society of Parkinson's disease (dpv)
- Michael J. Fox Foundation (MJFF)
- Movement Disorders Society
- Novartis
- European Union
- BMBF (the Federal Ministry of Education and Research)
- Helmholtz Association
- Michael J. Fox Foundation
- Robert Bosch Foundation
- Neuroalliance
- Janssen
- Boehringer Ingelheim
- Lundbeck Inc.
- GlaxoSmithKline
- UCB/SCHWARZ PHARMA
- Merck Serono
- Johnson Johnson
- Teva Pharmaceutical Industries Ltd.
- Solvay Pharmaceuticals, Inc./Abbott
- Boehringer
- UCB
- BMBF
- dPV (German Parkinson's disease association)
- Neuroallianz
- DZNE
- Center of Integrative Neurosciences
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Background: Parkinson's disease (PD) patients show a large phenotypic variability probably reflecting inter-individual pathologic heterogeneity. Next to typical Lewy-body pathology, beta-amyloid (A beta) and tau pathology have been found at autopsy and several studies have reported altered CSF levels of A beta 1-42, total-Tau (t-Tau) and phosphorylated-Tau (p-Tau). Objectives: To 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. Methods: In an explorative study we assessed CSF profiles of A beta 1-42, 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). Results: Compared to healthy controls, all three PD cohorts showed lower levels of A beta 1-42. 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. Conclusion: PD patients present with disease-specific CSF profiles of A beta 1-42, 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. (C) 2015 Elsevier Ltd. All rights reserved.
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