Alzheimer’s Disease in the year 2014 alone cost £24.2 billion (UK), but what can be done?

Alzheimer’s Disease is defined according to mass cerebral atrophy i.e. the loss of brain volume, alongside the deposition of a protein known as amyloid precursor protein, and the formation of a tangle within neurons due to the over modification of a second protein; tau.

In the absence of Alzheimer’s Disease, the amyloid precursor protein is processed at a certain position in the sequence to form a protein product which has no effect in the body. However in Alzheimer’s Disease, the same protein is processed at an alternative position leading to the formation of a protein which sticks to other proteins like glue. This leads to formation of a protein plaque which causes the death of neurons.

With regard to tau, tau acts as a key which fits the microtubule lock. In neurons, microtubules form long string-like structures essential in neuronal stability. In Alzheimer’s Disease the tau protein is over modified, so tau can no longer be the key to fit in the microtubule lock. The long string-like structure consequently intertwine with one another to form tangles, and result in the death of the neurons.

The treatment as of now focuses on inhibiting an enzyme called cholinesterase; cholinesterase breaks down acetylcholine. The neurons which die in Alzheimer’s release acetylcholine, so the treatment as of current aims to maintain acetylcholine levels by inhibiting the breakdown, to act as a compensatory method for the loss of acetylcholine producing neurons.

So what is the issue with this treatment? The treatment as of current is not a cure but instead only reduces the symptoms of Alzheimer’s Disease.

It is thereupon essential to take an alternative approach to treating Alzheimer’s Disease. There is a region within the neuronal cell called the endoplasmic reticulum; which functions in the forming of proteins and ensuring these proteins are in the correct shape. In Alzheimer’s Disease, the tau proteins being modified, and the formation of the protein plaque, means the proteins are not in the correct shape. This induces a state of stress.

Stress in the endoplasmic reticulum has implications on the unfolded protein response pathway. The activation of this pathway leads to one of two outcomes; cell neuronal death or a reduction in the endoplasmic reticulum stress. In Alzheimer’s Disease due to the abundance of proteins in an incorrect shape, this pathway becomes dysfunctional and the output switches to cell neuronal death. It is therefore possible to target a certain aspect of this pathway to inhibit the cell neuronal death and therefore treat Alzheimer’s Disease in a manner that relieves more than just the symptoms.

Is targeting the unfolded protein response pathway the future in Alzheimer’s Disease treatment? We can hope.