Decrease of Transthyretin Synthesis at the Blood-Cerebrospinal Fluid Barrier of Old Sheep

Abstract

Transthyretin (TTR), synthesized by the choroid plexus (CP) and secreted into cerebrospinal fluid (CSF), is involved in thyroxine (T4) transport and chelation of beta-amyloid peptide, attenuating neurotoxicity. To characterize age-related changes in TTR synthesis, CSF and CPs were collected from young adult (1-2 years) and old (>8 years) sheep anesthetized with thiopentone sodium. TTR in old sheep CSF was low compared to young (n = 4 each); however, CP messenger RNA (mRNA) for TTR did not change. CPs were perfused with Ringer containing 14C-leucine to assess de novo protein synthesis, or with 125I-T4 to assess T4 transport. Protein synthesis, including TTR, was reduced in old sheep CP and in newly secreted CSF. 125I-T4 Vmax and Kd (but not Km) were reduced in old sheep CP. These age-related changes suggest reduced capacity of CP to maintain CSF T4 homeostasis and could also reduce chelation of beta-amyloid and be an added risk for Alzheimer's disease.