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This Article Figures Only Full Text Full Text (PDF) CME: Take the course for this article: Volume 69, Number 16, October 16, 2007 All Versions of this Article: 01.wnl.0000271077.82508.a0v1 69/16/1569    most recent Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nielsen, H. M. Articles by Janciauskiene, S. M. Search for Related Content PubMed PubMed Citation Articles by Nielsen, H. M. Articles by Janciauskiene, S. M. Related Collections Alzheimer's disease Dementia with Lewy bodies

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

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.

Address correspondence and reprint requests to Dr. Sabina Janciauskiene, Lund University, Department of Clinical Sciences, Wallenberg Laboratory, 2nd Floor, Malmö University Hospital Entrance 46, SE-205 02 Malmö, Sweden sabina.janciauskiene{at}med.lu.se

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 ₁-antichymotrypsin and ₁-antitrypsin, and CSF levels of ₁-antichymotrypsin, ₁-antitrypsin, and neuroserpin along with three standard biomarkers (total tau, tau phosphorylated at threonine-181, and the Aß_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 ₁-antichymotrypsin and 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 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 ₁-antichymotrypsin, neuroserpin, and Aß_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 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.

GLOSSARY: AAT = ₁-antitrypsin; ACT = ₁-antichymotrypsin; AD = Alzheimer disease; ApoE = apolipoprotein E; AUC = area under the curve; BBB = blood-brain barrier; COPD = chronic obstructive pulmonary disease; %CV = coefficients of variation percentage; DLB = dementia with Lewy bodies; IL = interleukin; MMSE = Mini-Mental State Examination; NSAIDs = nonsteroidal anti-inflammatory drugs; OR = odds ratio; P-tau = tau phosphorylated at threonine-181; ROC = receiver operating characteristic; T-tau = total tau.

e-Pub ahead of print on August 29, 2007, at www.neurology.org.

Supported by the Swedish Research Council, the King Gustaf V and Queen Victoria Foundation, the Medical Research Council (UK), the Wellcome Trust, and Papworth NHS Trust.

Disclosure: The authors report no conflicts of interest.

Received January 6, 2007. Accepted in final form April 2, 2007.

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