Biochemical characteristics of variant transthyretins causing hereditary leptomeningeal amyloidosis

Shigeaki Mitsuhashi, Masahide Yazaki, Takahiko Tokuda, Yoshiki Sekijima, Yukihiko Washimi, Yuko Shimizu, Yukio Ando, Merrill D. Benson, Shu Ichi Ikeda

Research output: Contribution to journalArticle

23 Scopus citations


Transthyretin (TTR) is a tetrameric protein that can dissociate into amyloidogenic monomers and cause TTR-related amyloidosis. A rare phenotype, called hereditary leptomeningeal TTR amyloidosis, in which TTR amyloid deposition occurs mainly in leptomeninges and subarachnoid vessels, has been reported in patients with several different TTR variants. In the present study, we examined TTR variants immunoprecipitated from the serum and cerebrospinal fluid (CSF) of patients with hereditary leptomeningeal TTR amyloidosis using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (IP-Mass method). The leptomeningeal-type TTR variants were not detected in the serum but were found at low levels in the CSF. The undetectable levels of the leptomeningeal-type TTR variants in serum could explain the minute amounts of systemic deposition of these variants. The relatively high level of unstable TTR variants in CSF, probably due to increased secretion from the choroid plexus, is considered to be the pathogenesis of the leptomeningeal-type of TTR amyloidosis.

Original languageEnglish (US)
Pages (from-to)216-225
Number of pages10
Issue number4
StatePublished - Dec 1 2005


  • Hereditary leptomeningeal TTR amyloidosis
  • Instability of TTR tetramer
  • Mass spectrometry
  • Transthyretin
  • TTR tetramerization

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

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  • Cite this

    Mitsuhashi, S., Yazaki, M., Tokuda, T., Sekijima, Y., Washimi, Y., Shimizu, Y., Ando, Y., Benson, M. D., & Ikeda, S. I. (2005). Biochemical characteristics of variant transthyretins causing hereditary leptomeningeal amyloidosis. Amyloid, 12(4), 216-225.