Variant transthyretin in blood circulation can transverse the blood-cerebrospinal barrier: qualitative analyses of transthyretin metabolism in sequential liver transplantation.
BACKGROUND
Although the choroid6 plexus of the brain is one of the most important production sites of transthyretin (TTR), the metabolism of TTR secreted in cerebrospinal fluid (CSF) remains to be elucidated.


METHODS
To perform qualitative analysis of variant TTR in CSF of patients who underwent a sequential liver transplantation using an explanted familial amyloidotic polyneuropathy (FAP) ATTR Val30 Met patient's liver, levels and forms of TTR of the two patients were analyzed by means of enzyme linked immunosorbent assay (ELISA) and matrix-assisted laser desorption/time-of-flight mass spectrometer (MALDI/TOF-MS), respectively.


RESULTS
After the operation, variant TTR levels in serum increased, and in CSF, a significant peak of free form of ATTR Val30 Met was detected in the transplanted patients whose CSF had shown no variant TTR before the operation.


CONCLUSIONS
These findings suggest that the variant TTR can cross-the blood-CSF barrier and migrate into CSF from blood circulation. Because leptomeningeal amyloidosis occurs in FAP ATTR Val30 Met as the progression of the disease, this information suggests that in addition to peripheral neuropathy, disorders of the central nervous system (CNS) should be given an attention in patients who underwent sequential liver transplantation using an explanted FAP ATTR Val30 Met patient's liver.
Terazaki
H
H
First Department of Internal Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-0811, Japan.
Ando
Y
Y
Nakamura
M
M
Obayashi
K
K
Misumi
S
S
Shoji
S
S
Yamashita
S
S
Nakagawa
K
K
Ishizaki
T
T
Suhr
O
O
Uemoto
S
S
Inomata
Y
Y
Tanaka
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002199:Capillary Permeability / Q000502:physiology*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D011228:Prealbumin / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D011228:Prealbumin