New research suggests that vitamin A, previously associated with age-related cognitive impairment, could play a crucial role in the development of Alzheimer's disease.

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New research shows that mice deprived of vitamin A in the womb may have higher levels of beta amyloid (here shown as plaque in the brain of an Alzheimer's patient).

Alzheimer's disease is estimated to affect more than 5 million people in the United States, and it ranks as the sixth leading cause of death in the country.

While researchers recognize that, being a neurodegenerative disease, Alzheimer's is caused by the progressive death of cells, the exact reasons for this remain unknown.

Previous research has associated low levels of vitamin A with cognitive impairment. Some studies have suggested that vitamin A may help to protect neurobiological functions indirectly using the glucocorticoid pathway.

Others have suggested that vitamin A contributes to healthy memory processes, and they recommended a supplemental intake to prevent age-related cognitive impairment.

In this context, researchers from the University of British Columbia (UBC) in Canada hypothesized that vitamin A deprivation might play a role in the development of Alzheimer's disease.

So they set out to examine the impact of prenatal and infancy vitamin A deficiency on the development of Alzheimer's disease in mice, as these early stages are key for brain development. Additionally, the study examined the link between vitamin A and dementia in humans.

The study was a collaboration with Dr. Tingyu Li and others from the Children's Hospital of Chongqing Medical University in China. The team was led by Dr. Weihong Song, a professor of psychiatry at UBC and Canada Research Chair in Alzheimer's Disease.

The findings were published in the journal Acta Neuropathologica.

Vitamin A-deprived mice showed signs of prenatal damage

The scientists used genetically modified mice. They deprived some of these mice of vitamin A when they were still in the womb, while others were deprived postnatally through their diet. Some of the prenatally deprived mice were fed a normal diet, while others received vitamin A supplements. All of the mice were tested for learning and memory abilities.

Dr. Song and team found that a mild deficiency of vitamin A increased the levels of a protein called amyloid beta, and that vitamin A-deprived mice performed significantly worse on memory and learning tests when they grew up, compared with their healthy counterparts.

The beta-amyloid protein is known to play a key role in the advancement of Alzheimer's disease; it builds up into a sticky plaque or forms clumps between the nerve cells. This blocks the neurotransmission and eventually leads to the death of brain cells.

Furthermore, when the prenatally deprived mice were placed on a healthy diet as infants, they still performed worse in cognitive tests than mice that received a normal intake of vitamin A in utero, but were deprived postnatally. This suggests that the neural damage had started in the womb.

"Our study clearly shows that marginal deficiency of vitamin A, even as early as in pregnancy, has a detrimental effect on brain development and has [a] long-lasting effect that may facilitate Alzheimer's disease in later life."

Dr. Weihong Song

Interestingly, some of the damage appeared to be reversible - at least to some extent. The mice that were deprived prenatally but were given supplements of vitamin A right after birth had better learning and memory processing skills than mice who did not receive the supplements.

"In some cases, providing supplements to the newborn Alzheimer's disease model mice could reduce the amyloid beta level and improve learning and memory deficits," says Song. "It is a matter of the earlier, the better."

The researchers also examined the vitamin A-dementia link in humans. They investigated 330 seniors in Chongqing, China, and they found that 75 percent of the elders who had mild or significant vitamin A deficiency were also cognitively impaired, compared with 47 percent of those with healthy levels of vitamin A.

Despite the compelling results of the study, Dr. Song warns against exaggerating their significance. He points out that vitamin A deficiency is not very common in North America, and cautions against the dangers of an excessively high vitamin A intake. He urges pregnant women not to take vitamin A supplements in excess, and reminds them that the best way to maintain an ideal level of the vitamin is by having a balanced diet.

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