Transcobalamin Polymorphism and Serum Holo-Transcobalamin in Relation to Alzheimer’s Disease

Abstract

Isoforms of the vitamin B₁₂ carrier protein transcobalamin (TC) might influence its cellular availability and contribute to the association between disrupted single-carbon metabolism and Alzheimer’s disease (AD). We therefore investigated the relationships between the TC 776C>G (Pro259Arg) genetic polymorphism, total serum cobalamin and holo-TC levels, and disease onset in 70 patients with clinically diagnosed AD and 74 healthy elderly controls. TC 776C>G polymorphism was also determined for 94 histopathologically confirmed AD patients and 107 controls. Serum holo-TC levels were significantly higher in TC 776C homozygotes (p = 0.04). Kaplan-Meier survival functions differed between homozygous genotypes (Cox’s F-Test F(42, 46) = 2.1; p = 0.008) and between 776C homozygotes and heterozygotes (Cox’s F test F(46, 108) = 1.7; p = 0.02). Proportionately fewer TC 776C homozygotes appear to develop AD at any given age, but this will require confirmation in a longitudinal study.

Holotranscobalamin and Total Transcobalamin in Human Plasma: Determination, Determinants, and Reference Values in Healthy Adults

“…In our data set, the TCN2 766CϾG polymorphism was the strongest determinant of total TC concentrations, particularly when measured by ELISA. In contrast to published data (8,38 ), the effect of the TCN2 polymorphism on cobalamin or holoTC concentrations was nonsignificant except in women Ͼ45 years. Overall, our data suggest that it is important to take this polymorphism into account when studying associations between total TC and clinical outcome.…”

Levetiracetam for agitated Alzheimer's disease patients

“…This indicates that holo-TC encoded by the 776G allele might cross the blood-brain barrier less efficiently or be less stable in CSF and, hence, less efficient with regards to delivering vitamin B 12 to the brain than 776C-encoded holo-TC. Moreover, we recently showed that the 776G allele is associated with earlier age of onset of AD (McCaddon et al, 2004). Taken together, these findings suggest that improving the vitamin B 12 status of the elderly population by supplementation might postpone the development of AD in TC 776G homozygous and heterozygous individuals.…”

“…Since the 776G allele is associated with earlier age of onset of AD (McCaddon et al, 2004), our results warrant additional investigations addressing whether it is possible to delay the development of AD in individuals with 776CG and 776GG genotypes by highdose oral vitamin B 12 supplementation.…”

Effects of Folate and Vitamin B12 on Cognitive Function in Adults and the Elderly

“…No significant difference was reported when the three genotype groups were compared with each other or with the non-Parkinson's-disease participants. McCaddon et al [28] found that holotranscobalamin was significantly higher in persons with the CC genotypes than in those with the heterozygous CG genotype (p = .04). Postiglione et al [31] also found nonsignificant differences in vitamin B 12 levels when they analyzed according to subcategories of patients with Alzheimer's disease or controls who were homozygous for MTHFR C677T or nonhomozygous.…”