1. Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF
- Author
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Walter Boiten, Inger van Steenoven, Mei-Fang Xiao, Paul Worley, Barbara Noli, Cristina Cocco, Gian-Luca Ferri, Afina Lemstra, Charlotte Teunissen, Laboratory Medicine, Neurology, and Amsterdam Neuroscience - Neurodegeneration
- Subjects
Lewy Body Disease ,Male ,neuronal pentraxin 2 ,medicine.medical_specialty ,Nerve Tissue Proteins ,Inhibitory postsynaptic potential ,Article ,Cohort Studies ,chemistry.chemical_compound ,α-synuclein ,Internal medicine ,mental disorders ,Humans ,Medicine ,Cognitive Dysfunction ,Nerve Growth Factors ,Cognitive decline ,cerebral spinal fluid ,Spatial domain ,lcsh:QH301-705.5 ,cognitive function ,Aged ,Alpha-synuclein ,Cerebral Spinal Fluid ,business.industry ,Dementia with Lewy bodies ,biomarkers ,Cognition ,visual spatial domain ,General Medicine ,dementia with Lewy bodies ,Alzheimer’s disease ,VGF (non-acronym) ,Middle Aged ,medicine.disease ,nervous system diseases ,C-Reactive Protein ,Endocrinology ,lcsh:Biology (General) ,chemistry ,nervous system ,Case-Control Studies ,alpha-Synuclein ,GABAergic ,Female ,business - Abstract
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.
- Published
- 2020
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