Blood-based redox-signature and their association to the cognitive scores in MCI and Alzheimer’s disease patients

• Published in: Free radical biology & medicine 2019-01, Vol.130, p.499-511
• Main Authors: Perrotte, Morgane, Le Page, Aurélie, Fournet, Marianne, Le Sayec, Mélanie, Rassart, Éric, Fulop, Tamas, Ramassamy, Charles
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - pathology; Apolipoprotein D; Apolipoprotein J; Apolipoproteins D - blood; Biomarkers - blood; Brain - metabolism; Brain - pathology; Circulating-proteasome; Clusterin; Clusterin - blood; Cognitive Dysfunction - blood; Cognitive Dysfunction - pathology; Disease Progression; Female; Human health and pathology; Humans; Klotho; Life Sciences; Male; Membrane Proteins - blood; MMSE; MoCA; Oxidation-Reduction; Oxidative Stress - genetics; Proteasome Endopeptidase Complex - genetics; Protein oxidation; Reduced thiols; Total antioxidant capacity; Vitamin D - blood
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2018.10.452

Oxidative stress plays a pivotal and early role in the pathophysiology of Alzheimer's disease (AD). There is convincing evidence that oxidative alterations in AD and in mild cognitive impairment (MCI) patients are not limited to the brain but are extended to the blood compartment. However, the oxidative pattern in plasma is still inconclusive. Moreover, their potential association with the clinical scores MMSE (Mini-Mental State Examination) and MoCA (Montreal Cognitive Assessment) is poorly investigated. The aim of our study was to establish a pattern of blood-based redox alterations in prodromal AD and their evolution during the progression of the disease. Our results showed a reduction in the total antioxidant capacity (TAC) and an increase of the stress-response proteins apolipoprotein J (ApoJ) and Klotho in MCI subjects. For the first time, we evidenced circulating-proteasome activity. We found that the alteration of the circulating-proteasome activity is associated with the accumulation of oxidized proteins in plasma form early AD. Interestingly, the TAC, the levels of vitamin D and the activity of proteasome were positively associated to the clinical scores MMSE and MoCA. The levels of protein carbonyls and of ApoJ were negatively associated to the MMSE and MoCA scores. The levels of apolipoprotein D (ApoD) were not different between groups. Interestingly, the receiver operating characteristic (ROC) curves analysis indicated that these redox markers provide a fair classification of different groups with high accuracy. Overall, our results strengthen the notion that some specific oxidative markers could be considered as non-invasive blood-based biomarkers for an early MCI diagnosis and AD progression. [Display omitted] •Early Impairment of the plasma ability to degrade H2O2 in MCI patients.•Rise of some stress‐response proteins from the MCI status.•Inverse correlation between the circulating‐proteasome activity and protein oxidation in AD plasma.•Some plasma oxidative markers are linked to cognitive scores (MoCA and MMSE).•A combination of oxidative markers can be considered for the MCI diagnosis and the progression of AD.