Decrease of transthyretin synthesis at the blood-cerebrospinal fluid barrier of old sheep

Transthyretin (TTR), synthesized by the choroid plexus (CP) and secreted into cerebrospinal fluid (CSF), is involved in thyroxine (T-4) 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 C-14-leucine to assess de novo protein synthesis, or with I-125-T-4 to assess T-4 transport. Protein synthesis, including TTR, was reduced in old sheep CP and in newly secreted CSF. I-125-T-4 V-max and K-d (but not K-m) were reduced in old sheep CP. These age-related changes suggest reduced capacity of CP to maintain CSF T-4 homeostasis and could also reduce chelation of beta-amyloid and be an added risk for Alzheimer's disease.