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Connecting the dots: Biomarkers could be key to understanding Alzheimer’s

Connecting the dots: Biomarkers could be key to understanding Alzheimer’s

While there is no known cure for Alzheimer's currently, researchers are actively looking to identify biomarkers that can give them insights
Representational image | Shutterstock

When Delhi-based businessman Vivek Mittal started noticing that his 76-year-old mother was forgetting things regularly, he was annoyed – at first. For example, she would forget to do small things like pay the bills or talk about something unrelated to a subject. At other times, she would go into a monologue repeating the same things over and over again. However, Mittal’s perception changed when his mother was diagnosed with Alzheimer’s disease. 

“It made me realize that forgetting things was not her choice, but a result of the disease,” says Mittal. 

While there is no known cure for Alzheimer’s currently, disease progression can be delayed by managing the symptoms. Moreover, researchers are actively looking for ways to identify the early indicators or biomarkers that can give them insights into understanding the chances of how one could develop Alzheimer’s. 

Understanding Alzheimer’s   

Alzheimer’s disease is a progressively deteriorating neurological condition that causes the person affected to lose a sense of orientation, and the capacity to think, memorise, learn, and comprehend. Science has shown that this is because of the damage the brain’s neurons (nerve cells) suffer. A sticky substance (plaque) called amyloid beta builds up between nerve cells, disrupting neuron function. Moreover, another protein called tau gets accumulated within the cell and hardens it. In addition, the damage to the nerve cells is irreversible.   

Memory loss is a hallmark symptom of Alzheimer’s; people with the condition often find it challenging to remember names, including their own. Hence, as the condition advances, they find it difficult to perform day-to-day activities and become entirely dependent on caregivers. Research has shown that the triggers for Alzheimer’s can arise in multiple ways: from hereditary and non-hereditary factors, to lifestyle, and environmental factors.   

Is it in the genes? 

A recent study by a team from the Saha Institute of Nuclear Physics, Kolkata, has investigated why women are more prone to developing Alzheimer’s.  

Their analysis shows that when the early embryo is growing, a gene called IncRNA XIST is activated in the embryo. XIST acts on the egg from the female, silencing one copy of the X- chromosome, thereby bringing equality between the male and female chromosomes (XY and XX, respectively).  

“Abnormal activity of the XIST gene can be one of the reasons why women are much more predisposed to Alzheimer’s,” says Prof Debashis Mukhopadhyay, the study’s lead researcher, while speaking to Happiest Health.   

Other studies have found that mutation in other genes such as the Amyloid Precursor Protein, Presenilin, and APOE can cause aggregation of plaque-like amyloid. This happens because of improper breaking down and clearing of the amyloid-beta protein.  

A delicate balance 

When cells perform various activities, they release molecules called free radicals. These free radicals are highly reactive and can become toxic to the cells. As a counter measure, cells also produce neutralising agents called antioxidants that trap these unstable molecules and stop them from harming the cells. However, when excess free radicals build up in the cells, outweighing the level of antioxidants, it leads to what is known as oxidative stress in the cells. Oxidative stress can sound the death knell for neurons, worsening their degeneration.

A 2021 study in the Journal of Alzheimer’s Disease by researchers from the National Brain Research Centre in Gurgaon found that when an antioxidant called glutathione reduces, a specific brain region called the hippocampus turns alkaline. In other words, the electrical conductivity nature of the surroundings changes, thereby altering the nerve cell activity. As a result, nerve cells get damaged leading to cognitive impairment – the ability to remember, learn, think, and make decisions. Again, this possibly triggers the onset of Alzheimer’s.  

“In addition, if one is predisposed to Alzheimer’s, then oxidative stress can rapidly progress the disease,” says Dr Mukhopadhyay.  

When the brain’s scavenger cells don’t cooperate 

A July 2022  study in Nature Aging found that the malfunction of specific brain cells called microglia could induce the onset of Alzheimer’s. Microglia act as scavengers and prevent waste build-up in the brain. The study shows that impaired action of microglial cells was due to the improper trigger from a receptor protein, which in turn led to the aggregation of amyloid protein.  

Management mantras  

“Lifestyle plays a crucial role in delaying the progression of Alzheimer’s,” says Dr Sushma Chawla, the founder and president of Hope Ek A.S.H.A., an NGO working for the care of Senior Citizens with Alzheimer’s / Dementia (Memory Loss).  

She says regular physical activities such as exercise and yoga increase the nutrient and oxygen supply to the brain. Better nutrition implies healthier cells that will improve memory and cognition in people with Alzheimer’s. Besides, meditation helps manage stress by reducing the level of the stress hormone cortisol, calming the mind, she adds.    

Dr Mukhopadhyay concurs: “Activities such as learning a new language, solving puzzles, learning music, and so on, help strengthen the existing neurons and promote new neuron connections. This acts as a shield from neuronal damage.”

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