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Published online before print August 29, 2007, doi:10.1212/01.wnl.0000271077.82508.a0)
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 Volume 69, Number 16, October 16, 2007
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Received January 6, 2007
Accepted April 2, 2007

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

H. M. Nielsen MSc, L. Minthon MD, PhD, E. Londos MD, PhD, K. Blennow MD, PhD, E. Miranda PhD, J. Perez PhD, D. C. Crowther PhD, MRCP, D. A. Lomas PhD, FRCP, and S. M. Janciauskiene PhD*

From the Chronic Inflammatory and Degenerative Disease Research Unit (H.M.N., S.M.J.) and Clinical Memory Research Unit (L.M., E.L.), Department of Clinical Sciences, Lund University, Malmö University Hospital, Malmö, Sweden; Department of Clinical Neuroscience (K.B.), Section of Experimental Neuroscience, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden; and Department of Medicine (E.M., J.P., D.C.C., D.A.L.), University of Cambridge, Cambridge Institute for Medical Research, Hills Road, Cambridge, UK.


* To whom correspondence should be addressed. E-mail: sabina.janciauskiene{at}med.lu.se.

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.




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