Down-Regulation of Three Different Forms of Transthyretin in CSF from First-Onset, Drug-Naïve Schizophrenia Patients

<p>Examples of CSF spectra from healthy volunteers and patients with schizophrenia within 6–17 kDa are shown in (A). The peak cluster indicated (red cursor) is enlarged in (B). Statistical details of each sub-peak are listed in the table presented just below (B). On-chip reduction of CSF peptide/protein with β-mecaptoethanol at room temperature showed that the three peaks 13,741, 13,875, and 13,923 Da were reduced into a single peak (C), suggesting that they are different <i>S</i>-cysteinylated derivatives of the same protein. To identify the protein, CSF samples from a healthy volunteer and a patient with schizophrenia were applied to an anion exchanger column (HyperD, Ciphergen Biosystems) and eluted with pH 9–pH 3 buffers. A major ~14–15-kDa band was eluted in the pH 3 fraction (D, left panel). The protein was identified as transthyretin using LC-MS/MS (D, right panel) and the sequence coverage is shown in red. Note, that all the peptides shown have an <i>E-</i>score of < 0.05, indicating a high probability for the assigned protein identity. In addition, the band was confirmed to be the peak cluster at around 13.5–14 kDa in the spectra by eluting the protein(s) from the gel and SELDI analysis (E).