A potential treatment for Alzheimer’s disease: The Common Oral diuretic pill I Ashwini

Alzheimer’s disease, the most common cause of dementia, has taken the world by storm. As more people live longer lives, the chances of experiencing Alzheimer’s disease increases exponentially. The typical age of onset for Alzheimer's is 65 and older, affecting 1 in 14 people. It is estimated that by 2040, an astonishing number of 12.7 million people aged 65 and older will have Alzheimer’s disease. With such overwhelming statistics, I think it is needless to say that prevention should be prioritised.

Alzheimer’s disease affects the hippocampus, responsible for formation of memories. This means that most symptoms include memory loss, difficulties completing familiar tasks or mood disturbance, whilst late-stage symptoms include losing the ability to hold a conversation, difficulty moving or a lack of awareness of one’s surroundings.

To our understanding, Alzheimer’s disease is predominantly caused by complex changes to nerve cells in the brain leading to neurons eventually dying. These complex changes are caused by tau tangles and beta-amyloid plaques; abnormal levels of the naturally occurring beta-amyloid clump together to form plaques that collect between neurons and disrupt cell function. In addition, Tau tangles harm the synaptic communication between neurons. The abnormal build-up of proteins in and around brain cells is also a main contributor to the development of Alzheimer’s disease.

Together, these contribute to the neurodegeneration (death of neurons and synaptic connections) that results in the overall shrinkage (atrophy) of brain matter within the cortex and hippocampus. However, it must be noted that 5-10% of all cases are caused by genetic predisposition caused by inherited genetic mutations to key genes.

It is very important that we identify any risk factors as Alzheimer’s disease is irreversible. Currently, the known risk factors in daily life include: Age, Oxidative Stress, Beta-amyloid concentration. As the age of an individual increases, their chances of developing Alzheimer’s disease also increases. A by-product of energy production by cells, free radicals, is neutralised by antioxidants. In high concentrations, free radicals can damage cell membranes, causing tissue damage, thus requiring neutralisation by antioxidants. An imbalance between antioxidants and free radicals causes oxidative stress. Age-related Alzheimer’s disease is thought to be due to an accumulation of oxidative damage. Another risk factor is beta-amyloid plaques as the ability to clear such plaques dwindles with age.

Unfortunately, there is no single test to diagnose Alzheimer’s disease or any other dementia. Generally, if a GP is concerned that the symptoms may be due to dementia, they may refer you to a specialist. The specialist(s) will usually be a neurologist and/or psychiatrist at a dedicated memory clinic. A neurologist will assess for physical signs of dementia using a CT or MRI scan, whereas a psychiatrist will evaluate the cognitive symptoms. At the memory clinic, a standardised questionnaire called the mini mental state examination (MMSE) will be used to assess cognitive ability. This includes a set of 30 questions, in which a score greater than 24 indicates normal cognitive abilities.

An upcoming treatment for Alzheimer’s disease caused by genetic disposition is the common oral diuretic pill also known as bumetanide. Bumetanide tends to be used to treat fluid retention often caused by medical problems such as heart, kidney, and liver disease. Researchers have carefully scrutinised and analysed information in databases of brain tissue samples and FDA-approved drugs whilst investigating the effects of bumetanide on tau tangles and beta-amyloid plaques. They validated the data-driven discoveries by testing bumetanide in both mouse models of Alzheimer's and induced pluripotent stem cell-derived human neurons. They found that treating the mice which expressed the human APOE4 gene with bumetanide reduced memory deficits, implying that bumetanide does help reduce Alzheimer’s disease. Fortunately, the neutralising effects of bumetanide were also confirmed in the human models.

This life-changing discovery is bound to reduce the rate of Alzheimer’s cases but it should be taken into consideration that bumetanide is only effective in those with a genetic predisposition. As said by Jean Yuan, M.D., Ph.D., Translational Bioinformatics and Drug Development program director in the NIA Division of Neuroscience ‘Alzheimer's disease will likely require specific types of treatments, perhaps multiple therapies, including some that may target an individual's unique genetic and disease characteristics.’

Sources:

https://www.news-medical.net/news/20211011/Common-oral-diuretic-pill-may-be-a-potential-candidate-for-Alzheimers-treatment.aspx

Last accessed:

09/11/2021

Image and statistics taken from Alzheimer’s Association

https://www.alz.org/alzheimers-dementia/facts-figures

Last accessed on 12/12/2021