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Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF

Background: Dementia with Lewy bodies (DLB) is a neurodegenerative disease where synaptic loss and reduced synaptic integrity are important neuropathological substrates. Neuronal Pentraxin 2(NPTX2) is a synaptic protein that drives the GABAergic inhibitory circuit. Our aim was to examine if NPTX2 ce...

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Autores principales: Boiten, Walter A., van Steenoven, Inger, Xiao, Mei-Fang, Worley, Paul F., Noli, Barbara, Cocco, Cristina, Ferri, Gian-Luca, Lemstra, Afina W., Teunissen, Charlotte E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824459/
https://www.ncbi.nlm.nih.gov/pubmed/33383752
http://dx.doi.org/10.3390/cells10010038
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author Boiten, Walter A.
van Steenoven, Inger
Xiao, Mei-Fang
Worley, Paul F.
Noli, Barbara
Cocco, Cristina
Ferri, Gian-Luca
Lemstra, Afina W.
Teunissen, Charlotte E.
author_facet Boiten, Walter A.
van Steenoven, Inger
Xiao, Mei-Fang
Worley, Paul F.
Noli, Barbara
Cocco, Cristina
Ferri, Gian-Luca
Lemstra, Afina W.
Teunissen, Charlotte E.
author_sort Boiten, Walter A.
collection PubMed
description Background: Dementia with Lewy bodies (DLB) is a neurodegenerative disease where synaptic loss and reduced synaptic integrity are important neuropathological substrates. Neuronal Pentraxin 2(NPTX2) is a synaptic protein that drives the GABAergic inhibitory circuit. Our aim was to examine if NPTX2 cerebral spinal fluid (CSF) levels in DLB patients were altered and how these levels related to other synaptic protein levels and to cognitive function and decline. Methods: NPTX2, VGF, and α-synuclein levels were determined in CSF of cognitive healthy (n = 27), DLB (n = 48), and AD (n = 20) subjects. Multiple cognitive domains were tested, and data were compared using linear models. Results: Decreased NPTX2 levels were observed in DLB (median = 474) and AD (median = 453) compared to cognitive healthy subjects (median = 773). Strong correlations between NPTX2, VGF, and α-synuclein were observed dependent on diagnosis. Combined, these markers had a high differentiating power between DLB and cognitive healthy subjects (AUC = 0.944). Clinically, NPTX2 levels related to global cognitive function and cognitive decline in the visual spatial domain. Conclusion: NPTX2 CSF levels were reduced in DLB and closely correlated to decreased VGF and α-synuclein CSF levels. CSF NPTX2 levels in DLB related to decreased functioning in the visual spatial domain.
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spelling pubmed-78244592021-01-24 Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF Boiten, Walter A. van Steenoven, Inger Xiao, Mei-Fang Worley, Paul F. Noli, Barbara Cocco, Cristina Ferri, Gian-Luca Lemstra, Afina W. Teunissen, Charlotte E. Cells Article Background: Dementia with Lewy bodies (DLB) is a neurodegenerative disease where synaptic loss and reduced synaptic integrity are important neuropathological substrates. Neuronal Pentraxin 2(NPTX2) is a synaptic protein that drives the GABAergic inhibitory circuit. Our aim was to examine if NPTX2 cerebral spinal fluid (CSF) levels in DLB patients were altered and how these levels related to other synaptic protein levels and to cognitive function and decline. Methods: NPTX2, VGF, and α-synuclein levels were determined in CSF of cognitive healthy (n = 27), DLB (n = 48), and AD (n = 20) subjects. Multiple cognitive domains were tested, and data were compared using linear models. Results: Decreased NPTX2 levels were observed in DLB (median = 474) and AD (median = 453) compared to cognitive healthy subjects (median = 773). Strong correlations between NPTX2, VGF, and α-synuclein were observed dependent on diagnosis. Combined, these markers had a high differentiating power between DLB and cognitive healthy subjects (AUC = 0.944). Clinically, NPTX2 levels related to global cognitive function and cognitive decline in the visual spatial domain. Conclusion: NPTX2 CSF levels were reduced in DLB and closely correlated to decreased VGF and α-synuclein CSF levels. CSF NPTX2 levels in DLB related to decreased functioning in the visual spatial domain. MDPI 2020-12-29 /pmc/articles/PMC7824459/ /pubmed/33383752 http://dx.doi.org/10.3390/cells10010038 Text en © 2020 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Boiten, Walter A.
van Steenoven, Inger
Xiao, Mei-Fang
Worley, Paul F.
Noli, Barbara
Cocco, Cristina
Ferri, Gian-Luca
Lemstra, Afina W.
Teunissen, Charlotte E.
Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF
title Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF
title_full Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF
title_fullStr Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF
title_full_unstemmed Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF
title_short Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF
title_sort pathologically decreased csf levels of synaptic marker nptx2 in dlb are correlated with levels of alpha-synuclein and vgf
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824459/
https://www.ncbi.nlm.nih.gov/pubmed/33383752
http://dx.doi.org/10.3390/cells10010038
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