If a broader trial could establish the pathbreaking research at India's National Brain Research Center (NBRC) at Manesar, it can perhaps completely revolutionise the management of Alzheimer’s Disease (AD), which remains a big puzzle for the medical researchers worldwide today.
NBRC has developed a blood-based technique that could help very early detection as well as new tips for the disease management. The researchers at the NBRC have found certain biomarkers in the blood that could indicate an early presence of Alzheimer’s Disease disease.
A team led by Prof Pravat Mandal has reported low level of the antioxidant glutathione (GSH) and high iron level in the brain of Alzheimer’s patients. The research published in May 2023 in ACS
Chemical Neuroscience has concluded that having low GSH level and high iron level in the blood can be a serious risk factor for AD. This could be a good screening tool for the otherwise challenging disease but needs to be clinically validated on a larger population.
Alzheimer’s Disease
Alzheimer’s Disease, the most common form of dementia, is a progressive neurodegenerative condition that lead to a decline in mental function severe enough to disrupt daily life. Despite a lot of scientific research on the disease efforts to treat this condition has been frustrating and slow paced. Many therapeutic tests have been tried but there is still no cure that can reverse the progress of the disease.
Although the disease predominantly affects memory, other cognitive domains are also affected and they can sometimes be the presenting signs of the disease. Despite an advancement in symptomatic management, no treatment has been found that alters the course of neuro-degeneration that leads to Alzheimer’s Disease.
As per the latest WHO data, more than 55 million people have dementia worldwide, and over 60 percent of whom live in low-and middle-income countries. Every year, there are nearly 10 million new cases recorded across the world. India alone has about 6.5 million AD patients.
Dementia results from a variety of diseases and injuries that affect the brain. It is currently the seventh leading cause of death and one of the major causes of disability and dependency among older people globally.
Can blood test detect Alzheimer’s Disease?
The researchers at NBRC have discovered that Alzheimer’s patients have reduced level of antioxidant glutathione and higher amount of radical generator iron/metal ions level in the hippocampus area (memory control area and decision making area) of the brain. Their research found that in a healthy person the brain iron level does not change in the hippocampus area in various age group (18-72 years). Likewise, the brain antioxidant GSH level of healthy people too does not change in the normal case.
The researchers measured the blood GSH and metal ions of a limited the sample group of people. Blood GSH level of the same participants do not vary in various age groups. However, there is a significant depletion of GSH in the left hippocampus (LH) in patients AD) with an elevation of iron level in the AD patients. It has been established by the researchers that the AD patients have very low GSH level.
Hence, they almost reached in conclusion that GSH and iron distribution in the brain and blood are distinct in patients. Among healthy participants, the GSH level does not vary within different age groups, although age-related neuropsychological scores change within the healthy control category.
This research forms a basis for performing further age correlation studies in a larger cohort of patients with AD. In addition, the combined evaluation of GSH (in plasma) and iron (serum) level in the AD patients may provide a unique risk/susceptibility biomarker for the disease. “If you are 50 years or above you should get this combo blood test every 5 years,” says Prof Mandal.
Limitations of the study
Although this study is the first one to report the GSH and iron levels from blood and the brain, the sample size in the aging group is small. More healthy participants are needed in various age groups with a 10 year gap (41−50years), (51−60 years), ( 61−70 years), (71 −80 years) for baseline data. “This test needs to be validated involving more patients across the country and clinical trials for early AD patients with GSH supplementation and iron chelator is the need of the hour,” he adds.
Challenging Canvas
Early detection is the key for the future. Indirect measurements that use biomarkers can perhaps provide some insight. For decades, scientists have been debating on the causes of decline in cognitive issues.
But an effective treatment is still not around the corner. Researchers have been working on a compound that could prevent the formation of the amyloid plaques thought to be responsible for the disease. The brain has main cells called neurons and supporting cells called glia. In Alzheimer’s, neurons progressively decrease in number, probably because of the toxic effects of an accumulating protein called beta-amyloid.
While the specific causes of Alzheimer’s are not fully known, it is characterised by changes in the brain—including amyloid beta plaques and neurofibrillary, or tau, tangles—that result in loss of neurons and their connections. Oxidative distress is one of the possible factors and believed to play role in AD and it is related to the imbalance of master antioxidant, glutathione (GSH) and metallic deposition in the hippocampus of the brain.
Subsequently, uncontrolled radicals destroy the neuronal cells in the hippocampus area. Hippocampus is responsible for thinking and decision making. After several years of research an accelerated approval was given to two drugs. But till all the trials are completed the scientific validation of the drugs cannot be established.
What the researchers proposes
The researchers have proposed that the brain needs to be enriched with glutathione through supplementation and an iron chelator should be given to reduce the iron load and clinical trial for this must be started on an urgent basis.
—The author, Dr Vanita Srivastava, is an independent science and health writer. The views expressed are personal.
Read her previous articles here
(Edited by : C H Unnikrishnan)
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