Transferrin is a glycosylated metal-carrying serum protein. One of the biological functions of glycosylation is to regulate the life span of proteins, less glycosylation leading to a faster clearance of a protein from the circulation. In the case of transferrin, this would indirectly also influence iron homeostasis. Higher glycosylation has been demonstrated in patients with Parkinson's disease and rheumatoid arthritis. A genetic variant of transferrin, TfC2, occurs with increased frequency in patients with Alzheimer's disease (AD), rheumatoid arthritis, and other diseases associated with a free radical etiology. Investigations have so far not revealed the reason for the pro-oxidative qualities of TfC2. In this study the glycosylation of Tf in AD (TfC1 homozygotes and TfC1C2 heterozygotes) was compared with alcohol-induced dementia (AID) patients and nondemented, age-matched controls, using isoelectric focusing followed by blotting with anti-Tf antibodies. In TfC1 homozygotes a shift was found toward higher sialylation, but in TfC1C2 heterozygotes the 5- and 6-sialylated bands were less concentrated. The decreased sialalytion found for TfC1C2 heterozygotes, may indicate that the pro-oxidative TfC2 molecules are removed from the circulation at a faster rate than TfC1. This may be of benefit to AD patients having TfC2, but still does not explain why this Tf variant is pro-oxidative.

In relapsing-remitting MS subjects, serum iron concentration correlated significantly with age at diagnosis (r=0.49; p=0.008). In Caucasian female MS subjects, serum iron and ferritin concentrations were significantly lower than in matched controls. In a 6-month pilot study, 12 subjects taking a regimen of nutritional supplements designed to promote myelin regeneration, improved significantly neurologically as measured by the Kurzke EDSS (Total Score means 3.50 to 2.45, 29.9%; p=0.021). These were significantly improved (p=0.002) compared to 6 control group patients taking multivitamins (Kurzke Score increased by 13.9% from 4.83 to 5.50). Both groups had significantly reduced homocysteine concentrations at 6 months, suggesting that methylation is necessary but not sufficient for myelin regeneration.