title: Biochemical characteristics of variant transthyretins causing hereditary leptomeningeal amyloidosis.
abstract: 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.
authors.affiliation: Third Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Mitsuhashi
authors.forename: Masahide
authors.initials: M
authors.lastname: Yazaki
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tokuda
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sekijima
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Washimi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.forename: Merrill D
authors.initials: MD
authors.lastname: Benson
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Ikeda
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D028226:Amyloidosis, Familial / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000235:genetics; D002831:Choroid Plexus / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011228:Prealbumin / Q000032:analysis* / Q000134:cerebrospinal fluid* / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D011228:Prealbumin