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

Institute of Gerontology, King's College, London University, United Kingdom.

Address correspondence to Dr. R. L. Chen, Institute of Gerontology, Franklin-Wilkins Building, King's College, 150 Stamford Street, London SE1 9NH. E-mail: ronnie.chen{at}kcl.ac.uk

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