Indian scientists develop low-cost method to detect Alzheimer’s at early stage

Researchers at the Indian Institute of Science, Bengaluru have developed a low-cost method to detect Alzheimer’s at an early stage.

They have developed a small molecular fluorogenic probe that can sense a specific enzyme associated with the progression of Alzheimer’s disease.

The team claims that this could be made into a strip-based kit that could enable on-site diagnosis.

The details have been published in Analytical Chemistry, which states that early detection of Alzheimer’s disease is the key to taking appropriate measures against it.

Alzheimer’s disease is a progressive neurological disorder that affects millions of people worldwide and is characterized by a gradual decline in memory, thinking and cognitive abilities.

It is caused by the accumulation of two abnormal protein structures in the brain: beta-amyloid plaques and tau tangles. Beta-amyloid plaques are sticky clumps of protein fragments that accumulate between neurons, disrupting their communication and leading to cell death. Tau tangles, on the other hand, are twisted fibers of tau protein that build up inside neurons, impairing their ability to transport nutrients and essential molecules.

Debashish Das, a CV Raman postdoctoral fellow, along with Jagapreet Sidhu, assistant professor at IISc, have designed a tiny molecular probe that can sense a specific enzyme linked to the progression of Alzheimer’s disease.

“Our target is the enzyme acetylcholinesterase (AChE),” the researchers said, adding that studies have shown that in the early stages of Alzheimer’s disease, AChE levels become unbalanced, thus making it a potential biomarker for the disease.

Brain cells or neurons secrete neurotransmitters – molecules that instruct other cells to perform certain actions.

Acetylcholine (ACh) is one such neurotransmitter, its levels in our nervous system are tightly regulated by enzymes like AChE, which break it down into two parts – acetic acid and choline.

The team analyzed the crystal structures of the enzyme (AChE) and the substrate (ACh) and designed a synthetic molecule that mimics ACh.

The probe developed by the team has a structural element (quaternary ammonium) that specifically interacts with AChE, and another that binds to the active site in AChE and is digested (like natural AChE), giving off a fluorescent signal. Is.

They tested the new tool on commercially available AChE as well as on laboratory-produced human brain AChE expressed in bacteria.

“We now have a proof-of-concept and a lead. Our goal is to take this to translation in an Alzheimer’s disease model. For this, we need to modify the probe,” says Das.