TRANSMETHYLATIONS AND NEURODEGENERATIVE DISORDERS - A REVIEW

Cobalamin (Cbl) and folate are interdependent key factors for transmet hylations and for synthesis of DNA. There is growing evidence for a ne gative 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 se en as an age-related risk factor for neurodegeneration and dementia of Alzheimer type. Another major risk factor for the development of Alzh eimer's disease is the genotypic variant epsilon 4 of apoE. Since apoE is also known to inhibit cell proliferation and DNA synthesis, it is suggested that addition of apoE epsilon 4 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 ex ert neurodegenerative effects until late-life.