Can carotenoids in the brain protect against Alzheimer’s?

Carotenoids are thought to protect against Alzheimer’s disease because of their antioxidant properties and their accumulation in the brain. However, a new study from Tufts University is putting the theory into question.

More than a century has passed since the German physician Dr. Alois Alzheimer first presented evidence on the case of Auguste Deter, who at only 51 suffered from severe memory loss and other psychological changes. At autopsy, Dr. Alzheimer found his patient had severe shrinkage and abnormal deposits of the nerve cells.

“That was in 1906,” said nutritionist Annie Roe, a USDA researcher at Tufts University, who presented her laboratory’s findings on April 21 at Experimental Biology 2012 in San Diego. “There’s still disparity among scientists as to the etiology of this rapidly growing disease as we now know as Alzheimer’s disease.”

Currently, in the United States there are 5.3 million people with Alzheimer’s disease. Unless new methods of intervention are available, however, the number is expected to reach 16 million by 2050. While the cause of the disease is not known, the deposits that Dr. Alzheimer first noted are now known to be amyloid-beta peptide deposits.

These deposits, or plaques, are a “hallmark diagnostic feature” of Alzheimer’s disease. Within the same region amyloid-beta plaques are found, increased concentrations of oxidized proteins, lipids DNA are also observed. It’s not yet clear whether or not that these products of oxidative stress caused the amyloid-beta plaque build-up or vice versa.

However, Roe said, it is clear that oxidative damage promotes neurotoxicity and is involved in cognitive impairment. Epidemiological studies have found that a higher dietary intake of carotenoids from fruits and vegetables are associated with reduced risk of age-related chronic diseases including Alzheimer’s disease. Other studies measuring the concentration of carotenoids in plasma have found an inverse relationship with chronic diseases.

Fruits and vegetables are the major sources of carotenoids in the diet, the most common of which are beta-carotene and beta-cryptoxanthin—two provitamin-A carotenoids. There is also lycopene, lutein, and zeaxanthin, which have no vitamin A activity. There are several biological mechanisms being explored for carotenoids’ potential protection to the brain.

However, Roe explained that her laboratory research focuses on the role of antioxidants and their relationship to Alzheimer’s disease, clinically determined by increased cognitive impairment. Since Alzheimer’s affects brain tissue, the researchers’ study purpose was to determine the concentration and magnitude of lipid peroxidation in brains diagnosed with Alzheimer’s disease compared with age-matched controls.

The Tufts laboratory received brain tissue samples from the National Institute for Child Health and Human Development (NICHD) Brain and Tissue Bank for Developmental Disorders. The samples were obtained from 15 individuals with Alzheimer’s disease and half with no known dementia. The samples were from subjects in their late 70s or early 80s, most of whom were Caucasians. The samples were of four different brain regions: occipital cortex, frontal cortex, hippocampus, and auditory cortex. To assess lipid peroxidation, the researchers extracted malondialdehyde (MDA)—a marker of oxidative damage—through HPLC.

When looking at relative distribution of major carotenoids between Alzheimer’s disease and controls, the study found the provitamin A carotenoids contributed to a significantly higher percentage of total carotenoids in the Alzheimer’s brains compared to the controls. Non-provitamin-A carotenoids contributed to higher concentration in control brains compared to Alzheimer’s disease brains, but there was no statistically significant difference.

In addition, Roe said, the absolute concentrations of provitamin-A carotenoids were higher in Alzheimer’s diseased samples versus control samples. There was no difference in absolute concentrations of lutein, zeaxanthin, or lycopene. There was also no significant difference between malondialdehyde concentrations and carotenoid concentrations.

Consistent with findings of increased pro-vitamin A carotenoids, retinol (vitamin A) concentration was significantly greater in the Alzheimer’s disease brains. However, when the study looked at malondialdehyde concentrations, there was not a significant difference between the two groups.

The findings “were interesting but unexpected,” Roe said, adding that when she looked at each region separately, she saw the same pattern in the hippocampus, a region that is highly vulnerable to the disease.

Since prior research has shown both in cell culture and in clinical studies that vitamin A can have a positive effect on beta-amyloid aggregation, it is possible that caregivers or physicians confounded results. For example, they may have encouraged their patients after diagnosis to consume more fruits and vegetables. It may be that carotenoids are beneficial to the brain, but simply not after the disease has set in. Roe suggests future studies should include dietary intake assessments and target people with earlier stages of dementia.

“This is just a snapshot view of a small group of people at the end of life, so we can’t infer any type of causation and certainly should not interpret the results to mean that vitamin A is bad for the brain,” Roe said.

The study’s results contradicted that of previous research, also presented at the conference by Neal Craft of Craft Technologies, which found an age-related decline of carotenoids in elderly brains that suggested that diminishing levels may be associated with Alzheimer’s disease.

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