Untangling Alzheimer’s by Aleya Menon

As the ageing population increases, unsurprisingly, the occurrence of age-related diseases rises alongside it. The dilemma neurologists face is in the treatment and care of patients with dementia, especially of Alzheimer’s disease - a specific type of dementia that affects memory, behaviour and thought and progressively worsens over time. The rise in dementia has landed it as 5th most likely cause of death and within this category, Alzheimer’s disease contributes to 70% of the deaths cementing particularly how lethal it is.

So if dementia is so common in our elderly population, why is there no cure? Unlike other common diseases like high blood pressure (which affects 1 in 3 adults in the UK), Alzheimer’s disease and other dementias are much more complicated. Unlike high blood pressure, there is no clear cause however there are two main theories - the Tau hypothesis and the Amyloid hypothesis. As the cause is unclear and the nature of Alzheimer’s varies, treatments are more effective if personalised to the patient though this is also a challenge as Alzheimer’s is only diagnosed after death when the brain can be examined for tell-tale signs of Alzheimer’s like “amyloid plaques” or loss of nerve cells. The amyloid hypothesis suggests that the presence of the gene for amyloid precursor protein (APP) or for the specific form of apolipoprotein APOE4 (which fails to remove amyloid) causes the presence of amyloid plaques. Whereas, the tau hypothesis suggests that tau protein abnormalities cause the formation of “neurofibrillary tangles” within nerve cells in the brain, causing the cells to destroy themselves.

That’s why new breakthroughs in Alzheimer’s research are so exciting, recently an article by newscientist reported that a bacterium that is found to play a role in gum disease may also be involved in Alzheimer’s. A bulk of research has been devoted to the popular amyloid hypothesis and the drugs developed that focus on it fail more often than they succeed. There is even evidence of patients with amyloid plaques and neurofibrillary tangles with no effect on their memory, behaviour, or thoughts. With the constant failures of new drugs trying to target the formation of plaques, combined with skepticism from other scholars about how valid the amyloid/tau hypotheses are, fresh and new ideas of what may be the key to Alzheimer’s disease are much welcomed.

A study by Dominy, S. et al. found that toxic proteases (enzymes) secreted by P. gingivalis bacteria called gingipains can cause Alzheimer-like symptoms in the brain, especially interfering with Tau proteins. Evidence of gingipains have been seen in the brains of human Alzheimer’s patients. To study it further, mice were infected with P. gingivalis. Mice are used as they can model certain diseases that humans have with a high level of accuracy and therefore can be used to study the disease and possible cures. Mice that were infected with P. gingivalis experienced brain infection and amyloid production especially in the regions that are most commonly affected by Alzheimer’s disease. This also highlights another key characteristic of Alzheimer’s disease - infection. With infection comes the inflammatory response, a response by the immune system which occurs when there is damage to the tissue and is often accompanied by swelling. The inflammatory response is a key factor in many chronic conditions, especially cancer.

Upon discovering a possible link, a few treatments were shown to be effective on the mouse population, these possible treatments are known as “gingipain blockers” which has shown promising results. Inflammation was reduced, and already affected neurons were rescued and made healthy again. A vaccine is also beginning to be developed against the bacteria which has given promising results.

Despite the promising results, will there ever be a full cure for Alzheimer’s? As with every complicated disease, one treatment won’t fix all. The gingipain blockers only rescue damaged neurons, many of which will have already died before the disease may even be noticed or diagnosed properly. While possible treatments are continuously being discovered, there is still a long way to go in finding effective preventative measures to Alzheimer’s entirely.



Sources:

https://www.newscientist.com/article/2191814-we-may-finally-know-what-causes-alzheimers-and-how-to-stop-it/

https://www.alz.org/alzheimers-dementia/what-is-alzheimers

http://advances.sciencemag.org/content/5/1/eaau3333.full

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