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Plasma and CSF serpins in Alzheimer disease and dementia with Lewy bodies

Nielsen, Henrietta LU ; Minthon, Lennart LU ; Londos, Elisabet LU ; Blennow, Kaj; Miranda, Elena; Perez, Juan; Crowther, Damian; Lomas, David and Janciauskiene, Sabina LU (2007) In Neurology 69(16). p.1569-1579
Abstract
Objective: Serine protease inhibitors (serpins), the acute phase reactants and regulators of the proteolytic processing of proteins, have been recognized as potential contributors to the pathogenesis of Alzheimer disease (AD). We measured plasma and CSF levels of serpins in controls and patients with dementia. Methods: Using rocket immunoelectrophoresis, ELISA, and Luminex xMAP technology, we analyzed plasma levels of alpha(1)-antichymotrypsin and alpha(1)-antitrypsin, and CSF levels of alpha(1)-antichymotrypsin, alpha(1)-antitrypsin, and neuroserpin along with three standard biomarkers ( total tau, tau phosphorylated at threonine-181, and the A beta(1-42)) in patients with AD (n=258), patients with dementia with Lewy bodies (DLB; n=38),... (More)
Objective: Serine protease inhibitors (serpins), the acute phase reactants and regulators of the proteolytic processing of proteins, have been recognized as potential contributors to the pathogenesis of Alzheimer disease (AD). We measured plasma and CSF levels of serpins in controls and patients with dementia. Methods: Using rocket immunoelectrophoresis, ELISA, and Luminex xMAP technology, we analyzed plasma levels of alpha(1)-antichymotrypsin and alpha(1)-antitrypsin, and CSF levels of alpha(1)-antichymotrypsin, alpha(1)-antitrypsin, and neuroserpin along with three standard biomarkers ( total tau, tau phosphorylated at threonine-181, and the A beta(1-42)) in patients with AD (n=258), patients with dementia with Lewy bodies (DLB; n=38), and age- matched controls (n=37). Results: The level of CSF neuroserpin was significantly higher in AD compared with controls and DLB, whereas CSF alpha(1)-antichymotrypsin and alpha(1)-antitrypsin were significantly higher in both AD and DLB groups than in controls. Results from logistic regression analyses demonstrate a relationship between higher CSF levels of alpha(1)-antichymotrypsin and neuroserpin and increased predicted probability and odds ratios (ORs) of AD ( OR 5.3, 95% CI 1.3 to 20.8 and OR 3.3, CI 1.3 to 8.8). Furthermore, a logistic regression model based on CSF alpha(1)-antichymotrypsin, neuroserpin, and A beta(1-42) enabled us to discriminate between AD patients and controls with a sensitivity of 94.7% and a specificity of 77.8%. Conclusions: Higher CSF levels of neuroserpin and alpha(1)-antichymotrypsin were associated with the clinical diagnosis of Alzheimer disease (AD) and facilitated the diagnostic classification of AD vs controls. CSF serpin levels did not improve the diagnostic classification of AD vs dementia with Lewy bodies. (Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurology
volume
69
issue
16
pages
1569 - 1579
publisher
American Academy of Neurology
external identifiers
  • WOS:000250198800004
  • Scopus:35848937127
ISSN
1526-632X
DOI
10.1212/01.wnl.0000271077.82508.a0
language
English
LU publication?
no
id
d3801c16-5ec2-444c-8a3b-d61ba0642b2b (old id 621810)
date added to LUP
2007-12-18 13:52:37
date last changed
2016-10-13 04:37:17
@misc{d3801c16-5ec2-444c-8a3b-d61ba0642b2b,
  abstract     = {Objective: Serine protease inhibitors (serpins), the acute phase reactants and regulators of the proteolytic processing of proteins, have been recognized as potential contributors to the pathogenesis of Alzheimer disease (AD). We measured plasma and CSF levels of serpins in controls and patients with dementia. Methods: Using rocket immunoelectrophoresis, ELISA, and Luminex xMAP technology, we analyzed plasma levels of alpha(1)-antichymotrypsin and alpha(1)-antitrypsin, and CSF levels of alpha(1)-antichymotrypsin, alpha(1)-antitrypsin, and neuroserpin along with three standard biomarkers ( total tau, tau phosphorylated at threonine-181, and the A beta(1-42)) in patients with AD (n=258), patients with dementia with Lewy bodies (DLB; n=38), and age- matched controls (n=37). Results: The level of CSF neuroserpin was significantly higher in AD compared with controls and DLB, whereas CSF alpha(1)-antichymotrypsin and alpha(1)-antitrypsin were significantly higher in both AD and DLB groups than in controls. Results from logistic regression analyses demonstrate a relationship between higher CSF levels of alpha(1)-antichymotrypsin and neuroserpin and increased predicted probability and odds ratios (ORs) of AD ( OR 5.3, 95% CI 1.3 to 20.8 and OR 3.3, CI 1.3 to 8.8). Furthermore, a logistic regression model based on CSF alpha(1)-antichymotrypsin, neuroserpin, and A beta(1-42) enabled us to discriminate between AD patients and controls with a sensitivity of 94.7% and a specificity of 77.8%. Conclusions: Higher CSF levels of neuroserpin and alpha(1)-antichymotrypsin were associated with the clinical diagnosis of Alzheimer disease (AD) and facilitated the diagnostic classification of AD vs controls. CSF serpin levels did not improve the diagnostic classification of AD vs dementia with Lewy bodies.},
  author       = {Nielsen, Henrietta and Minthon, Lennart and Londos, Elisabet and Blennow, Kaj and Miranda, Elena and Perez, Juan and Crowther, Damian and Lomas, David and Janciauskiene, Sabina},
  issn         = {1526-632X},
  language     = {eng},
  number       = {16},
  pages        = {1569--1579},
  publisher    = {ARRAY(0x7f8c928)},
  series       = {Neurology},
  title        = {Plasma and CSF serpins in Alzheimer disease and dementia with Lewy bodies},
  url          = {http://dx.doi.org/10.1212/01.wnl.0000271077.82508.a0},
  volume       = {69},
  year         = {2007},
}