Transmethylations and neurodegenerative disorders: A review

Summary min (Cbl) and folate are interdependent key factors for transmethylations and for synthesis of DNA. There is growing evidence for a negative Cbl balance in elderly people and the human brain appears to be the most vulnerable tissue for Cbl deficiency. A negative Cbl balance thus increases the risk of cerebral deterioration and and is to be seen as an age-related risk factor for neurodegeneration and dementia of Alzheimer type. Another major risk factor for the development of Alzheimerʹs disease is the genotypic variant ε4 of apoE. Since apoE is also known to inhibit cell proliferation and DNA synthesis, it is suggested that addition of apoE ε4 in an aging individual with subclinical cerebral Cbl deficiency would slow the DNA synthesis down to a threshold below which the brain cells cease to function. Such an interaction could explain why an inherited variant of apoE does not exert neurodegenerative effects until late-life.