Transcobalamin polymorphism and serum holo-transcobalamin in relation to Alzheimer's disease.

Abstract

Isoforms of the vitamin B(12) 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.

• Authors: Andrew McCaddon, Kaj Blennow, Peter Hudson, Alan Hughes, Joan Barber, Rob Gray, Gareth Davies, John H H Williams, Jennifer Duguid, Alwyn Lloyd, Steve Tandy, Marge Everall, Howard Cattell, Anne McCaddon, Dick Ellis, Mona Palmer, Nenad Bogdanovic, Carl-Gerhard Gottfries, Henrik Zetterberg, Lars Rymo, Björn Regland
• Journal: Dementia and geriatric cognitive disorders (Dement Geriatr Cogn Disord) Vol. 17 Issue 3 Pg. 215-21 ( 2004) ISSN: 1420-8008 [Print] Switzerland
• PMID: 14739547 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2004 S. Karger AG, Basel

Chemical References

• Apolipoproteins E
• Vitamin B 12

Topics

• Aged
• Aging (physiology)
• Alzheimer Disease (blood, genetics, pathology)
• Apolipoproteins E (genetics)
• Female
• Genotype
• Heterozygote
• Homozygote
• Humans
• Male
• Middle Aged
• Polymorphism, Genetic
• Psychiatric Status Rating Scales
• Reverse Transcriptase Polymerase Chain Reaction
• Sex Characteristics
• Survival Analysis
• Vitamin B 12 (genetics)