Alzheimer’s Disease

Alzheimer’s disease is a degenerative neurological disease in which the patients increasingly lose their memory and become confused. It is the most common cause of dementia in the elderly. Nerve cells in the brain particularly in the hippocampus and the cerebral cortex, die and the levels of several neurotransmitters including acetylcholine 4.6, fall.

The loss of the nerve cells is accompanied by the formation of bamyloid plaques and neurofibrillary tangles. The plaques are formed from clumps of  β-amyloid protein that accumulate in the space between the nerve cells, while the tangles are found inside the nerve cells and are derived from a protein known as tau.

The acetylcholine deficiency cannot be remedied by just giving acetylcholine because it is too polar to cross the blood: brain barrier. Many of the current strategies are aimed at alleviating the symptoms by inhibiting the metabolism of acetylcholine in the brain. Acetylcholine is metabolized by hydrolysis of the acetate ester. Acetylcholine esterase inhibitors that are of value in this connection are tacrine (Cognex^®) 4.7, the daffodil alkaloid galanthamine (Reminyl^®) 4.8, donepezil hydrochloride (Aricept^®) 4.9 and rivastigmine (Exelon^®) 4.10. More recent targets have been to prevent th  β-amyloid protein undergoing cleavage in a way that initiates the formation of the  β-amyloid plaques. This  cleavage is brought about by a protease known as  β-secretase and a number of compounds have been identified, which inhibit the production of this enzyme. These include the spiroketal antibiotic, monensin.