The CNS-specific proteoglycan, brevican, and its ADAMTS4-cleaved fragment show differential serological levels in Alzheimer's disease, other types of dementia and non-demented controls: A cross-sectional study.
Evidence indicate that the brain-specific protein, brevican, is proteolytically cleaved during neurodegeneration, hence positioning fragments of brevican as potential blood biomarkers of neurodegenerative diseases, such as dementia. We aimed to develop two assays capable of detecting the brevican N-...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2020-01-01
|
Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0234632 |
id |
doaj-d8ed683ba0ae431bab3d7ead82ece9b2 |
---|---|
record_format |
Article |
spelling |
doaj-d8ed683ba0ae431bab3d7ead82ece9b22021-03-03T21:51:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01156e023463210.1371/journal.pone.0234632The CNS-specific proteoglycan, brevican, and its ADAMTS4-cleaved fragment show differential serological levels in Alzheimer's disease, other types of dementia and non-demented controls: A cross-sectional study.Ditte S JonescoMorten A KarsdalKim HenriksenEvidence indicate that the brain-specific protein, brevican, is proteolytically cleaved during neurodegeneration, hence positioning fragments of brevican as potential blood biomarkers of neurodegenerative diseases, such as dementia. We aimed to develop two assays capable of detecting the brevican N-terminal (N-Brev) and the ADAMTS4-generated fragment (Brev-A), cleaved at Ser401, in serum and to perform a preliminary assessment of their diagnostic potential in dementias. Monoclonal antibodies against N-Brev and Brev-A were used to develop two ELISAs detecting each epitope. A comparison of brevican fragments in serum from individuals with AD (n = 28), other dementia (OD) (n = 41), and non-dementia-related memory complaints (NDCs) (n = 48) was conducted. Anti-N-Brev and anti-Brev-A antibodies selectively recognized their targets and dilution and spike recoveries were within limits of ±20%. Intra- and inter-assay CVs were below limits of 10% and 15%, respectively. For the N-Brev biomarker, serum from patients with OD showed significantly lower levels than those with AD (p = 0.05) and NDCs (p < 0.01). The opposite pattern was evident for Brev-A: serum levels in patients with OD were significantly higher than for AD (p = 0.04) and NDCs (p = 0.01). For both N-Brev and Brev-A, levels did not differ between AD and NDCs. The ratio of N-Brev/Brev-A resulted in increased significant differences between OD and AD (p < 0.01) and between OD and NDCs (p < 0.0001). The ratio discriminated between NDCs and OD (AUC: 0.75, 95% CI: 0.65-0.85, p < 0.0001) and between OD and AD (AUC: 0.72, 95% CI: 0.59-0.85, p < 0.01). In conclusion, we developed the first assays detecting the N-terminal of brevican as well as an ADAMTS4-cleaved fragment of brevican in blood. Differential levels of N-Brev and Brev-A between AD and OD allow for these biomarkers to possibly distinguish between different forms of dementias.https://doi.org/10.1371/journal.pone.0234632 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ditte S Jonesco Morten A Karsdal Kim Henriksen |
spellingShingle |
Ditte S Jonesco Morten A Karsdal Kim Henriksen The CNS-specific proteoglycan, brevican, and its ADAMTS4-cleaved fragment show differential serological levels in Alzheimer's disease, other types of dementia and non-demented controls: A cross-sectional study. PLoS ONE |
author_facet |
Ditte S Jonesco Morten A Karsdal Kim Henriksen |
author_sort |
Ditte S Jonesco |
title |
The CNS-specific proteoglycan, brevican, and its ADAMTS4-cleaved fragment show differential serological levels in Alzheimer's disease, other types of dementia and non-demented controls: A cross-sectional study. |
title_short |
The CNS-specific proteoglycan, brevican, and its ADAMTS4-cleaved fragment show differential serological levels in Alzheimer's disease, other types of dementia and non-demented controls: A cross-sectional study. |
title_full |
The CNS-specific proteoglycan, brevican, and its ADAMTS4-cleaved fragment show differential serological levels in Alzheimer's disease, other types of dementia and non-demented controls: A cross-sectional study. |
title_fullStr |
The CNS-specific proteoglycan, brevican, and its ADAMTS4-cleaved fragment show differential serological levels in Alzheimer's disease, other types of dementia and non-demented controls: A cross-sectional study. |
title_full_unstemmed |
The CNS-specific proteoglycan, brevican, and its ADAMTS4-cleaved fragment show differential serological levels in Alzheimer's disease, other types of dementia and non-demented controls: A cross-sectional study. |
title_sort |
cns-specific proteoglycan, brevican, and its adamts4-cleaved fragment show differential serological levels in alzheimer's disease, other types of dementia and non-demented controls: a cross-sectional study. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2020-01-01 |
description |
Evidence indicate that the brain-specific protein, brevican, is proteolytically cleaved during neurodegeneration, hence positioning fragments of brevican as potential blood biomarkers of neurodegenerative diseases, such as dementia. We aimed to develop two assays capable of detecting the brevican N-terminal (N-Brev) and the ADAMTS4-generated fragment (Brev-A), cleaved at Ser401, in serum and to perform a preliminary assessment of their diagnostic potential in dementias. Monoclonal antibodies against N-Brev and Brev-A were used to develop two ELISAs detecting each epitope. A comparison of brevican fragments in serum from individuals with AD (n = 28), other dementia (OD) (n = 41), and non-dementia-related memory complaints (NDCs) (n = 48) was conducted. Anti-N-Brev and anti-Brev-A antibodies selectively recognized their targets and dilution and spike recoveries were within limits of ±20%. Intra- and inter-assay CVs were below limits of 10% and 15%, respectively. For the N-Brev biomarker, serum from patients with OD showed significantly lower levels than those with AD (p = 0.05) and NDCs (p < 0.01). The opposite pattern was evident for Brev-A: serum levels in patients with OD were significantly higher than for AD (p = 0.04) and NDCs (p = 0.01). For both N-Brev and Brev-A, levels did not differ between AD and NDCs. The ratio of N-Brev/Brev-A resulted in increased significant differences between OD and AD (p < 0.01) and between OD and NDCs (p < 0.0001). The ratio discriminated between NDCs and OD (AUC: 0.75, 95% CI: 0.65-0.85, p < 0.0001) and between OD and AD (AUC: 0.72, 95% CI: 0.59-0.85, p < 0.01). In conclusion, we developed the first assays detecting the N-terminal of brevican as well as an ADAMTS4-cleaved fragment of brevican in blood. Differential levels of N-Brev and Brev-A between AD and OD allow for these biomarkers to possibly distinguish between different forms of dementias. |
url |
https://doi.org/10.1371/journal.pone.0234632 |
work_keys_str_mv |
AT dittesjonesco thecnsspecificproteoglycanbrevicananditsadamts4cleavedfragmentshowdifferentialserologicallevelsinalzheimersdiseaseothertypesofdementiaandnondementedcontrolsacrosssectionalstudy AT mortenakarsdal thecnsspecificproteoglycanbrevicananditsadamts4cleavedfragmentshowdifferentialserologicallevelsinalzheimersdiseaseothertypesofdementiaandnondementedcontrolsacrosssectionalstudy AT kimhenriksen thecnsspecificproteoglycanbrevicananditsadamts4cleavedfragmentshowdifferentialserologicallevelsinalzheimersdiseaseothertypesofdementiaandnondementedcontrolsacrosssectionalstudy AT dittesjonesco cnsspecificproteoglycanbrevicananditsadamts4cleavedfragmentshowdifferentialserologicallevelsinalzheimersdiseaseothertypesofdementiaandnondementedcontrolsacrosssectionalstudy AT mortenakarsdal cnsspecificproteoglycanbrevicananditsadamts4cleavedfragmentshowdifferentialserologicallevelsinalzheimersdiseaseothertypesofdementiaandnondementedcontrolsacrosssectionalstudy AT kimhenriksen cnsspecificproteoglycanbrevicananditsadamts4cleavedfragmentshowdifferentialserologicallevelsinalzheimersdiseaseothertypesofdementiaandnondementedcontrolsacrosssectionalstudy |
_version_ |
1714814730418257920 |