TY  - JOUR
AU  - Lerche, Stefanie
AU  - Sjödin, Simon
AU  - Brinkmalm, Ann
AU  - Blennow, Kaj
AU  - Wurster, Isabel
AU  - Roeben, Benjamin
AU  - Zimmermann, Milan
AU  - Hauser, Ann-Kathrin
AU  - Liepelt-Scarfone, Inga
AU  - Waniek, Katharina
AU  - Lachmann, Ingolf
AU  - Gasser, Thomas
AU  - Zetterberg, Henrik
AU  - Brockmann, Kathrin
TI  - CSF Protein Level of Neurotransmitter Secretion, Synaptic Plasticity, and Autophagy in PD and DLB.
JO  - Movement disorders
VL  - 36
IS  - 11
SN  - 1531-8257
CY  - New York, NY
PB  - Wiley
M1  - DZNE-2022-00248
SP  - 2595 - 2604
PY  - 2021
AB  - Molecular pathways associated with α-synuclein proteostasis have been detected in genetic studies and in cell models and include autophagy, ubiquitin-proteasome system, mitochondrial homeostasis, and synaptic plasticity. However, we lack biomarkers that are representative for these pathways in human biofluids.The objective of this study was to evaluate CSF protein profiles of pathways related to α-synuclein proteostasis.We assessed CSF protein profiles associated with neurotransmitter secretion, synapse plasticity, and autophagy in 2 monocentric cohorts with α-synucleinopathy (385 PD patients and 67 DLB patients). We included 80 PD patients and 17 DLB patients with variants in the glucocerebrosidase gene to serve as proxy for accelerated α-synuclein pathology with pronounced clinical trajectories.(1) Proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy were lower in PD and DLB patients compared with healthy controls. (2) These patterns were more pronounced in DLB than in PD patients, accentuated by GBA variant status in both entities. (3) CSF levels of these proteins were positively associated with CSF levels of total α-synuclein, with lower levels of proteostasis proteins related to lower levels of total α-synuclein. (4) These findings could be confirmed longitudinally. PD patients with low CSF profiles of proteostasis proteins showed lower CSF levels of α-synuclein longitudinally compared with PD patients with a normal proteostasis profile.CSF proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy might serve as biomarkers related to α-synuclein proteostasis in PD and DLB. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
KW  - Autophagy
KW  - Biomarkers
KW  - Glucosylceramidase
KW  - Humans
KW  - Lewy Body Disease
KW  - Neuronal Plasticity
KW  - Neurotransmitter Agents
KW  - Parkinson Disease: metabolism
KW  - alpha-Synuclein: metabolism
KW  - CSF (Other)
KW  - GBA (Other)
KW  - PD (Other)
KW  - lysosome (Other)
KW  - secretion (Other)
KW  - synaptic plasticity (Other)
KW  - Biomarkers (NLM Chemicals)
KW  - Neurotransmitter Agents (NLM Chemicals)
KW  - alpha-Synuclein (NLM Chemicals)
KW  - Glucosylceramidase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:34180557
DO  - DOI:10.1002/mds.28704
UR  - https://pub.dzne.de/record/163488
ER  -