TY - JOUR
T1 - Pathologically decreased csf levels of synaptic marker nptx2 in dlb are correlated with levels of alpha-synuclein and vgf
AU - Boiten, Walter A.
AU - van Steenoven, Inger
AU - Xiao, Meifang
AU - Worley, Paul F.
AU - Lemstra, Afina W.
AU - Teunissen, Charlotte E.
N1 - Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/12/29
Y1 - 2020/12/29
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Biomarkers
KW - Cerebral spinal fluid
KW - Cognitive function
KW - Dementia with Lewy bodies
KW - Neuronal pentraxin 2
KW - VGF (non-acronym)
KW - Visual spatial domain
KW - α-synuclein
UR - http://www.scopus.com/inward/record.url?scp=85099226097&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cells10010038
DO - https://doi.org/10.3390/cells10010038
M3 - Article
C2 - 33383752
SN - 2073-4409
VL - 10
SP - 1
EP - 13
JO - Cells
JF - Cells
IS - 1
M1 - 38
ER -