NEW YORK (Reuters Health) Mar 01/2002 - In a mouse model of Alzheimer's disease, researchers have demonstrated that decreased intake of folic acid causes an increase in levels of homocysteine, which is associated with increased hippocampal neurodegeneration. Their report appears in The Journal of Neuroscience for March 1.

In an interview with Reuters Health, Dr. Mark P. Mattson, from the National Institute on Aging Gerontology Research Center in Baltimore, said that in their mouse model of Alzheimer's disease there were extensive amyloid deposits in the mouse brains. However, there was no evidence of neural degeneration while the mice received a normal diet, which was high in folate.

"The normal diet for these mice is equivalent to people taking folic acid supplementation," Dr. Mattson said. When he and his colleagues decreased the levels of folic acid they noted a degeneration of neural cells and cellular DNA damage. "This suggests that dietary folic acid deficiency may increase the risk for Alzheimer's disease," Dr. Mattson said.

When the mice were on the folate-deficient diet their homocysteine levels increased dramatically, he added. "Based on our experiments with these animals, the data suggest that it is the elevated homocysteine that leads to the degeneration of the nerve cells in the brain," Dr. Mattson said.

The combination of folate deficiency and increased homocysteine, "impair DNA repair in neurons, which sensitizes them to oxidative damage induced by amyloid beta-peptide," the researchers surmise.

Dr. Mattson added that "recent epidemiological data from the Framingham Heart Study, taken together with this study, show that there is a relationship between homocysteine levels and the risk for Alzheimer's disease and that increased homocysteine levels is sufficient to cause degeneration in nerve cells." (see Reuters Health report, February 13)

"People need to make sure that they get enough folic acid, whether through diet or supplementations. It is also important for individuals to know their homocysteine levels, and if they have high levels they should reduce them by taking folic acid and reducing calorie intake," Dr. Mattson advised.

J Neurosci 2002;22:1752-1762