Variant transthyretin in blood circulation can transverse the blood-cerebrospinal barrier: Qualitative analyses of transthyretin metabolism in sequential liver transplantation

Background. Although the choroid(6) 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 patients 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 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 patients liver.