Transthyretin: a choroid plexus-specific transport protein in human brain. The 1986 S. Weir Mitchell award.

TitleTransthyretin: a choroid plexus-specific transport protein in human brain. The 1986 S. Weir Mitchell award.
Publication TypeJournal Article
Year of Publication1986
AuthorsHerbert, J, Wilcox, JN, Pham, KT, Fremeau, RT, Zeviani, M, Dwork, A, Soprano, DR, Makover, A, Goodman, DS, Zimmerman, EA
Date Published1986 Jul
KeywordsAnimals, Brain Chemistry, Cattle, Choroid Plexus, Cloning, Molecular, DNA, Goats, Humans, Immunochemistry, Liver, Nucleic Acid Hybridization, Prealbumin, Protein Biosynthesis, Rabbits, Rats, Rats, Inbred Strains, RNA, Messenger

Plasma transthyretin (TTR, formerly called prealbumin) is a 55-kd protein that participates in the plasma transport of both thyroxine and retinol (vitamin A). TTR concentrations are disproportionately high in human ventricular CSF, suggesting that TTR is either selectively transported across or synthesized de novo within the blood-CSF barrier. To address this question, we adopted a molecular genetic approach; after isolating a cDNA clone encoding human TTR, we previously demonstrated specific TTR messenger RNA (mRNA) synthesis in rat choroid plexus. We have now extended these investigations to the human brain. Northern analysis of postmortem brain homogenates revealed abundant TTR mRNA in choroid plexus, but not in cerebellum or cerebral cortex. Choroid plexus mRNA was readily translated into TTR preprotein in an in vitro translation system. An immunocytochemical survey of human postmortem brain sections revealed the presence of TTR protein specifically and uniquely in the cytoplasm of choroid plexus epithelial cells; these results were corroborated at the mRNA level by an extensive survey of whole rat-brain sections by in situ hybridization. Therefore, within the mammalian CNS, TTR is the first known protein synthesized solely by the choroid plexus, suggesting a special role for TTR in the brain or CSF. Whether this function differs from its established plasma transport functions is presently unknown.

Alternate JournalNeurology
Citation Key10.1212/wnl.36.7.900
PubMed ID3714052
Grant ListAM27484 / AM / NIADDK NIH HHS / United States
NS07093 / NS / NINDS NIH HHS / United States
NS11766 / NS / NINDS NIH HHS / United States