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Departments of Neurology (Drs. Herbert, Zeviani, Zimmerman, and Schon, and Ms. Pham), Medicine (Drs. Soprano. Makover, and Goodman), and Pathology (Dr. Dwork), and the Center for Reproductive Sciences (Drs. Wilcox, Fremeau, and Roberts), Columbia University, College of Physicians and Surgeons, New York, NY; and the Office of the Chief Medical Examiner in the City of New York (Dr. Dwork).
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.
Address correspondence and reprint requests to Dr. Schon, Department of Neurology, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032.
Supported by Grants NS11766 to E.A.S., AM27484 to J.L.R., NS07093 to R.F., and HL21006 and AM05968 to D.S.G. from the National Institutes of Health; by Training Grants HD07093 from the National Institutes of Health to J.N.W. and NS07155 to J.H.; and by a grant to E.A.S. from the Muscular Dystrophy Association. J.H. and M.Z. are Fellows of the Muscular Dystrophy Association, and K.P. was a Muscular Dystrophy Association Summer Scholar.
Accepted for publication May 14, 1986.
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