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@ARTICLE{Lerche:163488,
author = {Lerche, Stefanie and Sjödin, Simon and Brinkmalm, Ann and
Blennow, Kaj and Wurster, Isabel and Roeben, Benjamin and
Zimmermann, Milan and Hauser, Ann-Kathrin and
Liepelt-Scarfone, Inga and Waniek, Katharina and Lachmann,
Ingolf and Gasser, Thomas and Zetterberg, Henrik and
Brockmann, Kathrin},
title = {{CSF} {P}rotein {L}evel of {N}eurotransmitter {S}ecretion,
{S}ynaptic {P}lasticity, and {A}utophagy in {PD} and {DLB}.},
journal = {Movement disorders},
volume = {36},
number = {11},
issn = {1531-8257},
address = {New York, NY},
publisher = {Wiley},
reportid = {DZNE-2022-00248},
pages = {2595 - 2604},
year = {2021},
abstract = {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.},
keywords = {Autophagy / Biomarkers / Glucosylceramidase / Humans / Lewy
Body Disease / Neuronal Plasticity / Neurotransmitter Agents
/ Parkinson Disease: metabolism / alpha-Synuclein:
metabolism / CSF (Other) / GBA (Other) / PD (Other) /
lysosome (Other) / secretion (Other) / synaptic plasticity
(Other) / Biomarkers (NLM Chemicals) / Neurotransmitter
Agents (NLM Chemicals) / alpha-Synuclein (NLM Chemicals) /
Glucosylceramidase (NLM Chemicals)},
cin = {AG Gasser / Core ICRU},
ddc = {610},
cid = {I:(DE-2719)1210000 / I:(DE-2719)1240005},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34180557},
doi = {10.1002/mds.28704},
url = {https://pub.dzne.de/record/163488},
}