Weihong Song. Photo credit: Martin Dee
The biochemical reactions that cause Alzheimer’s disease could be set in motion in the womb or just after birth if the fetus or newborn does not get enough Vitamin A, according to new research from the University of British Columbia.
Although it has long been known that Alzheimer’s disease unfolds in a person’s brain decades before symptoms appear, this is the first time the roots of the disease have been traced back to infancy or pre-natal development.
These new findings, based on studies of genetically-engineered mice, also demonstrate that supplements given to newborns with low levels of Vitamin A could be effective in slowing the degenerative brain disease.
Previous studies have implicated low levels of Vitamin A with Alzheimer’s disease. People with Alzheimer’s disease tend to have lower levels of that nutrient in their blood; a diet low in Vitamin A increases the risk of developing the condition; and rodents deprived of Vitamin A start to show signs of the disease.
Weihong Song, a Professor of Psychiatry, built off those previous studies by examining the effects of Vitamin A deprivation in the womb and infancy – crucial periods during which brain tissue is “programmed” for the rest of a person’s life. Dr. Song, a Canada Research Chair in Alzheimer’s Disease and the Jack Brown and Family Professor, used mice that were genetically engineered to be susceptible to Alzheimer’s disease.
Dr. Song, in collaboration with Tingyu Li and others at Children’s Hospital of Chongqing Medical University, found that even a mild Vitamin A deficiency exacerbated the production of amyloid beta, the protein fragment that forms plaques that smother and ultimately kill neurons in Alzheimer’s disease. He also found that such mice, when deprived of Vitamin A in the womb or as pups, performed worse as adults on a standard test of learning and memory.
Reinforcing the notion that the earliest stages of development could be the most important for brain development, mice who were deprived of Vitamin A through their mothers’ diet and were then given a normal diet as pups performed worse than mice who received a normal amount of the nutrient in the womb but were deprived after birth. In other words, the damage had already been done in the womb.
Still, Dr. Song and his collaborators also showed that some “rescue” is possible: Mice who were deprived in utero but then given supplements immediately after birth performed better than prenatally-deprived mice who weren’t given such supplements.
In addition to inducing production of amyloid beta, there is evidence that Vitamin A deficiency also interferes with the brain’s ability to clear it out.
The study, published today in Acta Neuropathologica, also included new evidence in humans of the Vitamin A-dementia connection in later years. Examining 330 elderly people in Chongqing, Song and his collaborators found that 75 per cent of those with either mild or significant Vitamin A deficiency had cognitive impairment (not necessarily Alzheimer’s disease), compared to 47 per cent of those with normal Vitamin A levels.
Dr. Song says China seems to account for a disproportionate share of the world’s Alzheimer’s disease burden, which might be attributable to the widespread starvation and malnutrition in that country more than a half-century ago.
However, Dr. Song cautions against overreacting to this news. Vitamin A deficiency, though common in many low-income regions of the world, is rare in North America, and excess intake of the nutrient could be harmful. Pregnant women in particular should not take excessive Vitamin A supplements. A balanced diet is the best way to ensure adequate levels of the nutrient, and the top food sources of vitamin A in the North America include dairy products, liver, fish, and fortified cereals, carrots, broccoli, cantaloupe, and squash.
Generally, Vitamin A levels are not routinely checked in standard physical examinations, including pre-natal care examinations for women. People concerned about their Vitamin A levels should consult the health professional who is providing their primary or pre-natal care.
A portion of the research was funded by the National Natural Science Foundation of China and Canadian Institutes of Health Research.