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CSF Protein Level o...
CSF Protein Level of Neurotransmitter Secretion, Synaptic Plasticity, and Autophagy in PD and DLB
- Article/chapterEnglish2021
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LIBRIS-ID:oai:gup.ub.gu.se/308654
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https://gup.ub.gu.se/publication/308654URI
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https://doi.org/10.1002/mds.28704DOI
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Subject category:art swepub-publicationtype
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Background Molecular pathways associated with alpha-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. Objective The objective of this study was to evaluate CSF protein profiles of pathways related to alpha-synuclein proteostasis. Methods We assessed CSF protein profiles associated with neurotransmitter secretion, synapse plasticity, and autophagy in 2 monocentric cohorts with alpha-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 alpha-synuclein pathology with pronounced clinical trajectories. Results (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 alpha-synuclein, with lower levels of proteostasis proteins related to lower levels of total alpha-synuclein. (4) These findings could be confirmed longitudinally. PD patients with low CSF profiles of proteostasis proteins showed lower CSF levels of alpha-synuclein longitudinally compared with PD patients with a normal proteostasis profile. Conclusion CSF proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy might serve as biomarkers related to alpha-synuclein proteostasis in PD and DLB. (c) 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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Sjödin, SimonGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xsjsim
(author)
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Brinkmalm, AnnGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbrian
(author)
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Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbleka
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Wurster, I.
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Roeben, B.
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Zimmermann, M.
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Hauser, A. K.
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Liepelt-Scarfone, I.
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Waniek, K.
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Lachmann, I.
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Gasser, T.
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Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe
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Brockmann, K.
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
(creator_code:org_t)
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In:Movement Disorders: Wiley36:11, s. 2595-26040885-31851531-8257
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Lerche, S.
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Sjödin, Simon
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Brinkmalm, Ann
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Blennow, Kaj, 19 ...
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Wurster, I.
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Roeben, B.
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Zimmermann, M.
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Hauser, A. K.
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Liepelt-Scarfone ...
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Waniek, K.
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Lachmann, I.
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Gasser, T.
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Zetterberg, Henr ...
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Brockmann, K.
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University of Gothenburg