Question

Previous studies have shown that Alzheimer's patients who also take beta-blockers tend to see a slower decline in their mental function.

            a) Why would overstimulation of AMPA receptors cause short-term memory deficits?

            b) Alzheimer’s is associated with neuron death. Why would overstimulation of AMPA receptors cause neurons to die?

            c) Previous studies had found that blocking the AMPA receptor alleviates the misfiring caused by amyloid plaques in the brain. Why wouldn’t it be a useful strategy to treat Alzheimer’s with AMPA receptor antagonists?

            d) Why might heart-disease/blood pressure medication work to slow down the decline of people with Alzheimer’s

Answer 1

a) Over-stimulation of AMPA receptors cause short-term memory deficits as it creates a situation called Excitotoxity. This refers to damaged nerve cells due to excessive stimulation by neurotransmitters. The AMPA gets overstimulated and over-activated due to this excitotoxity. A high level of calcium enter the cells and this leads to secretion of a number of enzymes. This is responsible for STM deficits.

b) Over-stimulation of receptors lead to neuron death because of the following reasons:

i) Neuronal loss caused by brain atrophy is a major process of Alzheimer's disease.

ii) Amyloid is said to cause neuronal cell death.This is because excess amount of Amyloid starts multiple cytotoxic mechanisms, which leads to increase in intracellular calcium level, oxidative stress and the cell-death increases. This increase in amyloid therefore results in a complex neuron death.

c) Blocking the AMPA receptor alleviates misfires caused by amyloid plaques in the brain. However, it wouldn't be a useful strategy to treat Alzheimer's because:

i) In 1995, genetic links related to early onset of Alzheimer's were discovered.

ii) Blocking the amloid plaques is just one of the many ways to prevent the decline of the cognitive process.

ii) The current development therefore focuses on metabolic changes, insulin resistance, brain inflammations, production of Tau protein and clearance of Amyloid.

d) Blood pressure medication works to slow down the decline of people with Alzheimer's as it has been found that people with high blood pressure and heart diseases are more likely to have Alzheimer's. This is because high blood pressure can damage small blood vessels in the brain, which would affect parts of the brain responsible for cognitive activities.