Effect of Acetylcholinesterase Inhibitors on the Cognitive Impairments in Transgenic Drosophila Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is characterized by neuronal loss, synaptic dysfunction, deposition of amyloid-beta (Aβ), and neurofibrillary tangles (NFTs). AD patients exhibit the loss of cholinergic neurons, leads to low levels of acetylcholine and increased activity of acetylcholinesterase which further reduces the levels of acetylcholine. It has now been established that acetylcholine plays a major role in controlling cognitive functions. A number of drugs have been reported to inhibit the activity of acetylcholinesterase, which can improve cognitive dysfunction in AD patients.

We have studied the effect of two commonly used acetylcholinesterase inhibitors (Galantamine and Rivastigmine) on the transgenic Drosophila model of AD.

The effect of rivastigmine and galantamine was studied on cognitive parameters (Odour choice index, Open field assay, Courtship index and memory loss). Molecular docking was also performed for rivastigmine (with Aβ42 and acetylcholinesterase) and galantamine (with Aβ42 and acetylcholinesterase).

Both drugs were found to be effective in reducing cognitive defects. However, it was unclear from the data obtained which drug was more effective. The results obtained from the docking studies showed a positive interaction with Aβ42 and acetylcholinesterase for both drugs.

Rivastigmine and galantamine are potent in reducing cognitive dysfunction in the transgenic AD flies expressing human Aβ42 in the neurons.