Folic acid could be key to prevention of Alzheimer's disease

Folic acid could play an essential role in protecting the brain against Alzheimer's disease and other degenerative disorders, according to a study by scientists at the National Institute on Aging.​

A study carried out on mice found that those with a folate-deficient diet had elevated levels of homocysteine​, an amino acid found in the blood which is thought to double the risk of Alzheimer's disease.

The findings could help researchers explain the biochemical mechanisms linking high blood levels of homocysteine and the risk of developing the disease.

In the study, published in the latest issue of the Journal of Neuroscience​, the investigators fed one group of mice with Alzheimer's-like plaques in their brains a diet that included normal amounts of folate, while a second group was fed a diet deficient in the vitamin.

The mice involved were transgenic, meaning they were bred with mutant genes that cause Alzheimer's disease (AD) in people. They develop AD-like plaques in their brains that kill neurons.

The researchers from the Institute counted neurons in the hippocampus, a region of the brain which is critical for learning and memory and is destroyed as plaques accumulate during Alzheimer's disease.

The investigators found a decreased number of neurons in the mice with the folic acid deficient diet. The scientists also discovered that mice with low amounts of dietary folic acid had elevated levels of homocysteine in the blood and brain. They suspect that increased levels of homocysteine in the brain caused damage to the DNA of nerve cells in the hippocampus.

In transgenic mice fed an adequate amount of folate, nerve cells in this brain region were able to repair damage to their DNA. But in the transgenic mice fed a folate-deficient diet, nerve cells were unable to repair this DNA damage.

"These new findings establish a possible cause-effect relationship between elevated homocysteine levels and degeneration of nerve cells involved in learning and memory in a mouse model of Alzheimer's disease,"​ said Mark Mattson, chief of the NIA's Laboratory of Neurosciences and the study's principal investigator.

People who have Alzheimer's disease often have low levels of folic acid in their blood, but it is not clear whether this is a result of the disease or if they are simply malnourished due to their illness. However, considering the emerging research, Dr Mattson suggests that consuming adequate amounts of folic acid - either in the diet or by supplementation - could be beneficial to the aging brain and help protect it against Alzheimer's and other neurodegenerative diseases.

Green leafy vegetables, citrus fruits and juices, whole wheat bread and dry beans are good sources of the vitamin. Since 1998, the US Food and Drug Administration has required the addition of folic acid to enriched breads, cereals, flours, corn meals, pastas, rice, and other grain products. However, because it can take a long time for the symptoms of Alzheimer's disease to surface, researchers speculate it will be many years before folate supplementation in food could affect the incidence of dementia in the United States. A human clinical trial is being planned.

In AD, plaques develop first in areas of the brain used for memory and other cognitive functions. They consist of largely insoluble deposits of a protein called beta-amyloid. Although researchers still do not know whether amyloid plaques themselves cause AD or whether they are by-products of the AD process, there is evidence that amyloid deposition may be a central process in the disease.

But unlike human brain cells, the brain cells in laboratory mice are not killed by the progressive accumulation of beta amyloid. This finding led Dr Mattson and his research team to suspect folic acid or some other component of the mouse diet might help these nerve cells resist beta amyloid damage.

In earlier work, Dr Mattson found evidence suggesting folic acid deficiency can increase the brain's susceptibility to Parkinson's disease.