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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 ( p  = 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 ( r  = 0.387,  p  < 0.0001) and posterior cingulate ( r  = 0.196,  p  = 0.034). HO-1 values increased with increasing GMV at the uncus ( r  = 0.307,  p  = 0.0008), lateral globus pallidus and putamen ( r  = 0.287,  p  = 0.002), and hippocampus ( r  = 0.197,  p  = 0.034). IRE1 values decreased with increasing GMV at the uncus ( r  = −0.239,  p  = 0.010) and lateral globus pallidus and putamen ( r  = −0.335,  p  = 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.

diagnostics

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