DETECTION OF DIFFERENT FORMS OF VARIANT TRANSTHYRETIN (MET30) IN CEREBROSPINAL-FLUID

To detect the variant transthyretin (TTR; Met30) in cerebrospinal flui d (CSF) of familiar amyloidotic polyneuropathy (FAP) patients, we have applied a new method using a centrifugal concentrator device and elec trospray ionization mass spectrometry (ESI-MS). Only 100 mu l of CSF a nd 30 mu l of the antibody for TTR was needed for the analysis. After preparation of the samples with anti-TTR antibody, they were passed th rough a 1000 kDa cut-off centrifugal concentrator which retained the a ntibody. By analyzing the obtained filtrate with ESI-MS, three predomi nant forms of normal and their variant forms of TTR were detected in C SF samples. TTR (Met30), with a molecular weight 32.0 Da higher than t he normal form of TTR, was found in all FAP patients' materials. Altho ugh the ratio of the three major peaks of TTR were different in each i ndividual, they were always found in CSF and sera. This method will co ntribute to make a diagnosis of neurologic disorders having a mutant p rotein in CSF as well as serum. (C) 1997 Elsevier Science Ireland Ltd.