Relationship between brain tissue loss and levels of blood biomarkers in patients with Alzheimer’s disease

Abstract

AbstractBackgroundThe heme oxygenase‐1 (HO‐1) is known as up‐regulator in AD. The peptidylprolyl isomerase A (PPIA) (also known as cyclophilin A, CyPA) provides protection of neurons against copper‐mediated oxidative stress. The inositol‐requiring enzyme 1 (IRE1) is a major stress transducer in endoplasmic reticulum (ER) stress and abnormal protein aggregation. There is no study to evaluate the relationship between gray matter volume (GMV) loss and the three blood‐based biomarkers. Therefore, in this study, we evaluated the relationship between imaging biomarker by GMV changes and blood biomarkers by plasma levels of HO‐1, PPIA, and IRE1 in the groups of cognitively normal (CN), amnestic mild cognitive impairment (MCI), and AD participants.MethodWe obtained MRI and plasma levels of the three blood biomarkers from 45 CN, 34 amnestic MCI, and 39 AD. To assess the relationship between GMV or WMV loss and the three blood biomarkers, the voxel‐based multiple regression analysis was performed for using all participant data. In addition, region‐of‐interest (ROI)‐based analysis was performed to determine correlations between ROI‐based brain tissue volumes and plasma biomarkers. To investigate the relationship between GMV or WMV at each ROI and the plasma levels of HO‐1, PPIA, and IRE1, we performed the Pearson correlation analyses.ResultThe CypA value was significantly positively correlated with MMSE scores. The HO‐1 value was significantly negatively correlated with age, but was positively correlated with the K‐MMSE score. The IRE1 value was significantly positively correlated with age, but was negatively correlated with K‐MMSE scores. GMV was positively correlated with CypA and HO‐1, but negatively correlated with IRE1.ConclusionOur study demonstrates that subjects with AD have lower circulating levels of HO‐1 than subjects with MCI and the plasma HO‐1 levels were positively associated with the global GMV. This also shows that subjects with AD have lower circulating levels of CyPA than cognitively normal control and the plasma CyPA levels were positively associated with the GMV whereas subjects with AD have higher circulating levels of IRE1 than subjects with MCI and normal control.