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

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.