Relationship between Brain Tissue Changes and Blood Biomarkers of Cyclophilin A, Heme Oxygenase-1, and Inositol-Requiring Enzyme 1 in Patients with Alzheimer's Disease.

Cyclophilin A (CypA), heme oxygenase-1 (HO-1), and inositol-requiring enzyme 1 (IRE1) are believed to be associated with Alzheimer's disease (AD). In this study, we investigated the association between gray matter volume (GMV) changes and blood levels of CypA, HO-1, and IRE1 in cognitively normal (CN) subjects and those with amnestic mild cognitive impairment (aMCI) and AD. Forty-five elderly CN, 34 aMCI, and 39 AD subjects were enrolled in this study. The results of voxel-based multiple regression analysis showed that blood levels of CypA, HO-1, and IRE1 were correlated with GMV on brain magnetic resonance imaging (MRI) in the entire population ( = 0.0005). The three serum protein levels were correlated with GMV of signature AD regions in the population as a whole. CypA values increased with increasing GMV in the occipital gyrus ( = 0.387, < 0.0001) and posterior cingulate ( = 0.196, = 0.034). HO-1 values increased with increasing GMV at the uncus ( = 0.307, = 0.0008), lateral globus pallidus and putamen ( = 0.287, = 0.002), and hippocampus ( = 0.197, = 0.034). IRE1 values decreased with increasing GMV at the uncus ( = -0.239, = 0.010) and lateral globus pallidus and putamen ( = -0.335, = 0.0002). Associations between the three serum protein levels and regional GMV indicate that the blood levels of these biomarkers may reflect the pathological mechanism of AD in the brain.