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 se creted 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 familia l amyloidotic polyneuropathy (FAP) ATTR Val30 Met patients liver, levels an d forms of TTR of the two patients were analyzed by means of enzyme linked immunosorbent assay (ELISA) and matrix:-assisted laser desorption/time-of-f light mass spectrometer (MALDI/TOF-MS), respectively. Results. After the operation, variant TTR levels serum increased, and in CS F, a significant peak of free form of ATTR Val30 Met was detected in the tr ansplanted patients whose CSF had shown no variant TTR before the operation . Conclusions. These findings suggest that the variant TTR can cross-the bloo d-CSF barrier and migrate into CSF from blood circulation. Because leptomen ingeal amyloidosis occurs in FAP ATTR Val30 Met as the progression of the d isease, this information suggests that in addition to peripheral neuropathy , disorders of the central nervous system (CNS) should be given an attentio n in patients who underwent sequential liver transplantation using an expla nted FAP ATTR Val30 Met patients liver.