Cobalamin as a regulator of serum and cerebrospinal fluid levels of normal prions

We have previously demonstrated that the concentration of normal prion proteins (PrP^C) is increased in the serum and cerebrospinal fluid (CSF) of rats deficient in vitamin B₁₂ (cobalamin, Cbl). In this study, we investigated whether similar increases also occur in the serum and CSF of patients deficient in Cbl (Cbl-D), and whether the increase in serum levels can be corrected by Cbl therapy. The study involved two sample populations. The first consisted of 45 patients (13 patients with pernicious anemia [PA], 19 with other forms of anemia, and 13 healthy controls); and the second, 68 patients (five with subacute combined degeneration [SCD], 18 with amyotrophic lateral sclerosis, 22 with multiple sclerosis [MS], and 23 neurological controls). Serum PrP^C levels were measured using an enzyme-linked-immunosorbent-assay before as well as after Cbl therapy. The mean serum PrP^C levels in patients with PA were significantly higher than those of the controls (p = 0.0017) but normalized after Cbl therapy; there was no significant change in the patients with other forms of anemia. Mean CSF PrP^C levels in the patients with SCD were significantly higher than in the neurological controls (p <0.03). The serum and CSF PrP^C levels of patients with PA and those with SCD were correlated significantly with serum (p = 0.004) and CSF (p = 0.0018) Cbl levels. In patients with MS, CSF PrP^C concentrations were significantly lower than those of the controls regardless of their CSF Cbl levels. We found a correlation between Cbl and PrP^C levels in the serum and CSF of Cbl-D patients, which suggests that Cbl may regulate the PrP^C levels in the serum and CSF in humans.