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It’s a puzzle that has baffled scientists for long. The brain, which has an impenetrable protective layer around it in the form of a thick blood-brain barrier, should not be affected that easily by the chemical changes taking place elsewhere in the body. The blood-brain barrier, composed of tightly packed cells, insulates the brain from an overload of undesirable chemicals that circulate in the bloodstream, while still allowing the essential metabolic functions.
This is thought to be true in the case of blood sugar as well. Diabetes patients, who have high levels of glucose in their blood because of faulty insulin production, normally have near-normal glucose levels in the blood circulating through the myriad blood vessels in the brain.
Yet scientists have found that 30 to 65 per cent of diabetics run the risk of developing Alzheimer’s disease — a debilitating degenerative brain disorder that severely impairs cognitive function and memory — in their old age. The connection between the two, though circumstantial, has so far perplexed researchers.
The issue is of critical importance to India which may soon be the diabetes capital of the world. With the number of diabetes cases in the country rising, there may be an increase in the occurrence of Alzheimer’s disease, as has been happening in the West. Despite being the focus of the medical world for long, there is no cure for this severest form of dementia.
But a team of researchers at the Salk Institute of Biological Studies in the US seems to have resolved the puzzle. The scientists, led by David Schubert, claim to have found a molecular basis for the diabetes-Alzheimer’s interaction.
Though the brain remains largely insulated from the high blood sugar otherwise found in the body, the layers of the blood-brain barrier — which is composed of cells that are more densely packed than elsewhere in the body — are often exposed to the high blood sugar. As a result, the central nervous system is indirectly affected, scientists hypothesise.
To investigate this, Schubert — a professor at the institute’s Cellular Neurobiology Laboratory — and his colleagues studied the blood vessels in the brain of young mice that were rendered diabetic. The study, reported in the latest issue of Neurobiology of Aging, looked specifically at the interaction between the elevated blood glucose levels and beta-amyloid — protein molecules that clump together to form the senile plaques that riddle Alzheimer’s patients’ brains.
To their surprise, the scientists found that despite having beta-amyloid in very low levels — not enough to trigger the brain disorder — the mice began suffering from significant memory loss. They also noticed an increase in inflammation in the brain. “The damage took place long before the first plaques appeared,” says Schubert.
The mice suffered damage to the blood vessels well before any overt signs of Alzheimer’s — such as nerve cell death or the acquisition of amyloid deposits, the hallmark of the disease — could be detected in their brains. Further experiments revealed that the vascular damage was due to the overproduction of free radicals, resulting in oxidative damage to the cells lining the brain’s blood vessels.
“Because of the elevated blood glucose in diabetes, the blood vessels of the brain become damaged. This damage will lead to more stress in the brain because the availability of nutrients in the blood is reduced. Since nerve cells in the early stages of Alzheimer’s disease are themselves weakened, the additional stress of a poor nutrient supply may lead to their premature death, resulting in early onset of Alzheimer’s,” Schubert told KnowHow.
According to Joseph Burdo, co-author of the study, researchers earlier could not find a link between the two because they were looking for a direct connection between an impaired insulin signalling and Alzheimer’s, which never existed. “Many studies have focused on altered insulin signalling in the brain as a possible mechanism for the association between Alzheimer’s disease and diabetes but researchers paid much less attention to the impact of increased blood glucose levels on brain function and the pathogenesis of Alzheimer’s,” explains Burdo.
While it is normal for a person to have a low level of amyloid circulating in his or her blood, in diabetics there may be a synergistic toxicity between the amyloid and high level of blood glucose which comes in the way of proper blood vessel formation, says Burdo.
Anoop Misra, who heads the department of diabetes and metabolism at the Fortis Group of Hospitals, New Delhi, says that though it is too early to say the study may have any clinical significance, there is a lesson to take home. “If you could keep your blood sugar well under control, you can deal with two monsters — diabetes and Alzheimer’s.”
And that would be much like the proverbial stone that can kill two birds with one shot.
While there is no clear-cut study to establish the prevalence of Alzheimer’s disease in the Indian population, scientists infer that cases of the neurodegenerative disease may be far fewer in India than in the West despite increased life expectancy because of the amount of haldi (turmeric) Indians consume. A team of researchers at the Salk Institute of Biological Sciences in the US has now discovered that a downstream derivative of curcumin, the active ingredient in turmeric, does enhance cognition and memory. In a recent work published in Neurobiology of Aging, the scientists report isolation of the compound (called CNB-001), saying that it boosts communication between brain cells, facilitating long-term retention of memory. They feel that it could be a potential remedy for treating brain disorders affecting memory and cognition such as Alzheimer’s and Parkinson’s disease.
Sources: The Telegraph (Kolkata, India)