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Journalism of Courage
Certain bio-markers or indicators in the blood can help track the progression of Alzheimer’s disease — a neuro-degenerative condition associated with ageing. A group of researchers in the US are creating a bio bank of patient samples that can help codify these markers, which can help in early diagnosis, laying a template for preventive neurology.
This way people can be diagnosed in the doctor’s office and adopt lifestyle changes to slow disease progression. Dr Pravat Mandal, faculty of neurological surgery at University of Pittsburgh and former head of the National Brain Research Centre in India, talks about why there is a need for blood tests to diagnose and track progression of Alzheimer’s. He is not associated with the study but has extensively worked on Alzheimer’s disease.
An estimated 5.3 million people in India are living with dementia, Alzheimer’s being its most common form. This is likely to increase to 14 million by 2050.
The database will track around 100 people — either with family history of the disease, early stage mild cognitive impairment or healthy controls with no family risk — for years. Participants will come in for follow-ups every year or once in two years. Their blood will be drawn and tested for nearly 100 different protein markers.
This, the researchers say, will help them develop a benchmark for a blood-based Alzheimer’s test — essentially laying the foundation for simple blood tests akin to a blood glucose test for diabetes or a lipid test to check for high cholesterol levels. Currently, no one knows what levels of proteins commonly associated with Alzheimer’s (Amyloid B protein, Tau protein) definitively shows that one has the disease.
Regular testing will also help in keeping a track of the impact of interventions such as lifestyle modification, use of statins or GLP-1 drugs, new anti-amyloid therapies among others.
At present, a diagnosis of Alzheimer’s disease requires tests for physical and cognitive abilities, brain imaging or tests of spinal fluid. “A blood test would make it easier to diagnose people and be far less invasive or costly to track disease progression. This kind of study is much needed,” says Dr Mandal.
“There is also a need to move away from just amyloid beta protein and tau protein. While it is well-known that these proteins are abnormally present in the brains of Alzheimer’s patients, they may just be a symptom of the disease. If the cause is something different, then there is a need to look for other bio-markers which can tell us a person is likely to get Alzheimer’s even before they do — just like we tell people with pre-diabetes that they are heading towards diabetes,” he adds.
“Nearly 34% of all clinical trials for Alzheimer’s disease focuses on two proteins. However, there are different hypotheses that are coming up now,” says Dr Mandal.
The inflammatory hypothesis suggests that chronic inflammation in the brain leads to the progression of the disease. The gut-brain axis theory suggests that changes in the gut microbiome lead to the intestine becoming more permeable, triggering brain inflammation. The abnormal autophagy hypothesis suggests that the process that cells use to eliminate damaged parts — in this case the abnormal amyloid beta protein and tau protein — gets affected. And, the metal-ion hypothesis suggests that increased cell damage in the brain leads to Alzheimer’s disease.
Dr Mandal’s studies have shown that there is a dip in the level of an antioxidant called glutathione in the brains of those with Alzheimer’s and even early stage mild cognitive impairment. “Over the course of one’s life, there is an increasing deposition of iron in the brain, which is a free-radical generator. An imbalance between the free radicals and the antioxidant leads to Alzheimer’s,” he says.
