Biomarkers for Alzheimer’s

About 10 million new cases of dementia are diagnosed worldwide every year, of which, 60% to 70% are Alzheimer’s Disease (AD), as per the World Health Organisation (WHO). AD is the most common cause of dementia which leads to a gradual decline in memory, thinking, behaviour, and social skills. Hence, it is obvious that the disease needs to be diagnosed early for effective interventions.

However, it is challenging to diagnose AD in its early stages because it often goes unnoticed until symptoms become significant. The gold standard for diagnosis is a pathological analysis of the brain tissue of the patient which is invasive and not practical. The other methods are Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) scans which are expensive. Cerebrospinal fluid analysis for molecular biomarkers is another diagnostic technique that is invasive.

What are biomarkers?

Early diagnosis with biomarkers or biological markers is a less invasive and non-expensive method that is currently feasible. Biomarkers are devices used to evaluate biological markers in body fluids like blood, saliva, and urine.

In AD, diagnostic biomarkers focus on three pathologic features: abnormal amyloid beta peptide accumulation, abnormally phosphorylated tau-protein, and nonspecific neuronal degeneration. The most extensively evaluated plasma AD biomarkers are the plasma amyloid- (A), especially amyloid beta 42 and amyloid beta 40, and the phosphorylated tau (p-tau) protein at epitopes 181, 217, and 231. 

Accumulation of amyloid plaques in the brain is a hallmark of Alzheimer’s dementia. Studies have shown that certain forms of amyloid beta peptides, such as amyloid beta 42, are elevated in the blood.

What do Indian researchers say about AD biomarkers?

Indian researchers are looking for the imbalance of certain prevalent biomarkers specific to AD, using surface-enhanced Raman spectroscopy (SERS) and nanoparticle probes to classify blood samples as “healthy”, with mild cognitive impairment (MCI) and dementia. They are very close to perfecting the clinical validation of a diagnostic platform, which will enable the early detection of AD through a simple and affordable blood test.

The estimated dementia prevalence for adults aged 60+ in India is 7.4%. The average survival rate of Alzheimer’s is 3 to 9 years. This would translate into a huge burden on the society. Hence, the need of the hour is early diagnosis at a pre-clinical stage. Nevertheless, we are on the threshold of an exciting era where artificial intelligence and new body fluid-based biomarkers, in combination with other risk factors, will provide a novel solution that will revolutionise the early diagnosis of AD. 

Blood-based biomarkers for the diagnosis of Alzheimer’s are all the more important as the newer interventions with disease-modifying properties like Aducanumab and Lecanemab act at their best in the early stages of the disease.

(The author is a consultant neurologist and stroke physician.)