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

• Published in: The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2005-07, Vol.60 (7), p.852-858
• Main Authors: Chen, Ruo L., Athauda, Senarath B. P., Kassem, Nouhad A., Zhang, Yi, Segal, Malcolm B., Preston, Jane E.
• Format: Article
• Language: English
• Subjects: Aging; Aging - physiology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animals; Biological Transport - physiology; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Blood-Brain Barrier - metabolism; Blotting, Northern; Blotting, Western; Choroid Plexus - metabolism; Electrophoresis, Agar Gel; Gene Expression Regulation; Iodine Radioisotopes; Nervous system; Polymerase Chain Reaction; Prealbumin - biosynthesis; Prealbumin - cerebrospinal fluid; Prealbumin - genetics; Proteins; Ribonucleic acid; RNA; RNA, Messenger - metabolism; Sheep; Spectrophotometry; Thyroxine - metabolism
• ISSN: 1079-5006; 1758-535X
• DOI: 10.1093/gerona/60.7.852

Transthyretin (TTR), synthesized by the choroid plexus (CP) and secreted into cerebrospinal fluid (CSF), is involved in thyroxine (T4) transport and chelation of β-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 β-amyloid and be an added risk for Alzheimer's disease.