Redox-reactive antiphospholipid antibody differences between serum from Alzheimer's patients and age-matched controls

Abstract

There is no universally acceptable inclusive laboratory biomarker for the diagnosis and staging of neurodegenerative diseases, for example, Alzheimer's. There is an abnormal increase of oxidative stress in the central nervous system (CNS) of Alzheimer's patients that causes oxidation of proteins, lipids and DNA. We have published that the antiphospholipid (aPL) autoantibodies that are members of the redox-reactive autoantibody (R-RAA) family, are significantly decreased or absent in the cerebrospinal fluids of autopsy-confirmed Alzheimer's disease (AD) patients. Because of the known elevation of oxidation-induced damage in the CNS and the abnormal enrichment of redox reactive metals in postmortem AD brains, we questioned if the R-RAA in the blood of AD patients might also show a departure from the normal aPL levels. We compared 16 AD serum samples to 17 serum samples, from age-matched volunteer blood donors. Each serum was tested before and after oxidation for four aPL specificities by using an in-house ELISA. Comparisons between the AD and normal populations revealed highly significant differences. In-sample Fisher's linear discriminate analysis found a sensitivity of 88% and a specificity of 94%. In-sample Classification and Regression Tree analysis (CART) found a sensitivity of 84% and a specificity of 100%. This study is the first to indicate that blood tests for R-RAA may be used as a laboratory criterion for an Alzheimer's diagnosis.

Keywords::

• antiphosphatidylethanolamine
• biomarkers cognitive impairment
• dementia
• hemin
• redox-reactive autoantibodies
• unmasking autoantibodies

Acknowledgements

We thank Dr. Steve DeKosky for reading and providing constructive comments to our manuscript.

Declaration of interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.