Transthyretin Decrease in Plasma of MCI and AD Patients: Investigation of Mechanisms for Disease Modulation

Carlos      A. Ribeiro; Isabel      Santana; Catarina      Oliveira; Ines      Baldeiras; Jorge      Moreira; Maria      Joao Saraiva; Isabel      Cardoso

Abstract

Different authors described that transthyretin (TTR) is decreased in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) patients and thus TTR is a potential CSF biomarker in AD. However, descriptions of what happens to TTR in plasma of these patients are lacking in the literature. We investigated TTR levels in plasma samples from 55 patients with mild-cognitive impairment (MCI), 56 patients with AD and 41 non-demented controls, and found that TTR is decreased in both MCI and AD groups, suggesting that TTR might be used for staging early AD. In MCI and AD groups, women showed significantly lower plasma TTR levels when compared to MCI and AD men, respectively, and to women control group. In the AD women group, TTR levels correlated with disease stage, reflecting disease severity. Although MCI and AD men groups presented TTR levels lower than men in the control group, the difference was not statistically significant. Genetic analysis for ApoE revealed no relationship between TTR levels and the presence of the ε4 allele, for both men and women, in both patient groups. Importantly, we assessed thyroxine binding to TTR in plasma and found, in both MCI and AD groups, that TTR had reduced capacity to carry the hormone. Finally, we measured plasma estradiol levels in women and showed a reduction in both groups. Thus, this study prompts TTR as an early plasma biomarker in AD indicating that disease modulation by TTR is gender dependent; this study provides hypotheses into the mechanisms involved.

Keywords: Alzheimer’s disease, ApoE, biomarker, disease severity, estradiol, plasma, transthyretin, thyroxine