Affiliations: [a] Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden | [b] Section of Geriatric Psychiatry, University of Heidelberg, Heidelberg, Germany | [c] Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
Correspondence:
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Correspondence to: Aristi P. Fernandes, Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden. Tel.: +46 8 58582926; Fax: +46 8 58581020; E-mail: [email protected].
Abstract: Oxidative stress has an important role in the pathological process of most neurodegenerative disorders, including Alzheimer's disease (AD). The glutaredoxin (Grx) and thioredoxin (Trx) systems are central in maintaining a reduced environment in the cell and thus render protection against oxidative stress. Here, we show that Trx1 and Grx1 were released to the cerebrospinal fluid in 120 cases examined, and that the levels of these proteins increased significantly in the early stages of AD in comparison to mild cognitive impairment (MCI). Trx1 and Grx1 levels correlated with the established AD biomarkers tau and phospho-tau (p-tau). Moreover, by determining the levels of Trx1 and Grx1, discrimination between MCI converters and patients with stable MCI were possible. By applying the protein levels of Trx1 together with conventional diagnostic markers (Mini-Mental State Examination, tau, and p-tau) to a stepwise regression model, MCI stable, MCI converter, mild AD, and moderate AD was correctly diagnosed in 32 out of 33 cases. In order to further evaluate the involvement of these systems in AD, the immunoreactivity of Trx1, Trx2, Grx1, and Grx2 were investigated and the expression pattern was shown to be altered in hippocampus tissue sections from AD patients compared to controls. In conclusion, we introduce members of the thioredoxin super family of proteins as promising early biomarkers in the diagnosis of AD, suggesting their potential involvement in the pathogenesis of the disease.
