Dementia: Where are the answers?

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The human brain is made up of 100 billion nerve cells and is the most complex structure that we know of in the entire universe. This implausible organ makes us who we are. Our thoughts, emotions, personalities and memories are all thanks to the network of trillions of connections these cells make. However, the sheer dependence we have on our brains makes it so devastatingly vulnerable.

Dementia affects over 850,000 people in the UK alone. Many of us think of dementia as a “disease”, yet it is, instead, a term used to describe a group of symptoms that occur as a result of brain cell damage. There are many types of dementia, with multiple different causes and symptoms, which are generally associated with memory loss, confusion, personality change and communication difficulties. As the most common cause of dementia in the UK (affecting 62% of those diagnosed), a cure, or method of delaying its onset, for Alzheimer’s disease should undoubtedly be a priority.

What causes Alzheimer’s?

No one knows what the fundamental causes of Alzheimer’s disease are. However, it is known that it is caused by plaques and tangles of proteins that form in the brain. Some researchers believe the onset of these abnormalities are due to factors such as age, genetics and poor heart health, although it is agreed that the progression of Alzheimer’s is not a normal aspect of ageing.

The plaques are formed from a protein called Beta-amyloid. This protein normally plays an important role in neural growth and repair, and normally folds together by bonding between the amino acids (building blocks of proteins) of the molecule in its tertiary structure. This variety of different bonds forms between R-groups (variable chemical groups) on the amino acids as they can interact when the protein folds (this brings the groups closer to each other). However, when the protein does not fold together correctly and the R-groups are exposed, they start to clump together with other protein molecules (nucleating), causing the plaques.

These clusters of amyloid can then trigger other proteins to misfold and cluster together, creating oligomers. These oligomers are highly toxic and can block cell synapses, activating an auto-immune response that destroys the brain cells. This, in turn, leads to brain degradation.

The tangles are caused by the protein Tau, which collapses into the twisted strands. Normally, Tau creates a cell transport system, which can allow food molecules and other key materials to move along, to supply the cells. However, when these break down, the essential substances can no longer move to or through the cells, and so die.

This damage caused by the plaques and tangles spreads through the cerebral cortex in a predictable pattern but the time of progression, from mild to severe dementia, can be between two and 10 years. The cortex includes the main area of conscious thoughts and memory. In severe dementia, the brain shrinks due to severe damage in the cortex and the individual becomes unable to communicate, recognize family or care for themselves.

A possible cure?

As a leading cause of dementia, it incontestably should be a priority to find a cure for Alzheimer’s disease. Compared to other aspects of medicine, Alzheimer’s treatment is almost identical to what it was 111 years ago, when Alois Alzheimer described the first clinical case of dementia. Whilst cancer treatment has advanced from basic, unanaesthetized surgical removal to high-tech radiotherapy and chemotherapy, Alzheimer’s has made no progression.

However, with projections stating that by 2051 there will be two million dementia patients in the UK, there is an urgent need to develop a cure. The extra cost to the economy compared to research investment is unnecessary. Currently, for each dementia patient, £90 goes toward research. Yet, dementia costs the UK £26 billion per year– that’s £30,000 per patient- with unpaid carers saving the UK economy a further £11 billion. To put this in to perspective, cancer affects less than half the number of dementia patients, and only costs the annual economy £15.8 billion, but £176 per person affected is spent on research.

Research into Alzheimer’s clearly needs an increase in spending; there has been some interesting, and promising, research from the University of Cambridge already. In 2015, they found out that a molecule called Brichos acts as a “molecular chaperone”, helping to stop the plaques from producing oligomers. The molecule works by binding to the amyloid fibrils (plaques), and preventing them from supporting the misfolding of other proteins. In tests with living mouse brain tissue, the amyloid plaques were allowed to develop with both the molecular chaperone present and absent (as a control). When it was present, the results show that the plaques still formed but the toxic oligomers did not. Despite the research being in its early stages, results like these show how a drug could potentially block the secondary nucleation stage in the development of Alzheimer’s.

Another potential treatment for Alzheimer’s is to aid the body’s own immune system in removing these plaques and tangles in the brain. Researchers from the Queensland Brain Institute have found a way of combining immunotherapy with ultrasound to trigger an immune response. It works by targeting the Tau tangles and amyloid plaques with specific antibodies, and helps them cross the blood-brain barrier (a semi-permeable, selective membrane), by using ultrasound to open it up and causing it to “leak”. These antibodies alert the brain’s white blood cells, which can then remove the tangles and plaques, to an extent.

This early research is very promising for the future of Alzheimer’s treatment. With dementia patients set to rise considerably in the coming decades, there will be an unprecedented strain on the economy and NHS. Our brains are our greatest asset and so, as a society, we need to radically change our thinking and invest to prevent dementia. We must not accept that dementia is an inevitable part of ageing,  and we must fight it, striving just as hard as we would against cancer.