In 2015, 48 million people were living with Alzheimer’s disease worldwide. Currently, there is no effective treatment or cure for the disease – eagerly anticipated results from a recent drug study by Ely Lilly unfortunately showed another drug did not work. Dr Tara Spires-Jones from the Basic Science domain in the Centre for Dementia Prevention explains how solanezumab showed huge promise in earlier trials in dealing with Alzheimer’s disease pathology in the brain but the disease progress may have been too far along for the drug to be effective. Tara emphasises that the key aspect in Alzheimer’s research is identifying and targeting at risk population years before any symptoms occur. The interview is up on Inside Science on BBC Radio 4.
Role of amyloid plaques in the brain
Tara explains that there are a combination of factors in the brains of people with Alzheimer’s disease – genetic, environmental and foremost age. The combination of risk factors causes an increase in the amount of a protein called amyloid beta (abeta) in the brain. Abeta accumulates into clumps that are referred to as amyloid plaques in the brain. While in a normal brain, protein is soluble and runs around the cells, degenerative diseases like Alzheimer’s disease make protein clump. Tara explains it like going from liquid egg to solid scramble egg. These amyloid plaques themselves seem inert but they are surrounded by a halo of soluble forms of abeta which interacts with neurons. What abeta does is binding brain communication channels called synapses. Abeta is toxic to brain health and starts killing synopses. Synopses, however, allow plasticity, learning and memory to happen – Tara concludes that if the synapse function is damaged, a person’s ability to learn and remember is damaged too.
The recently tested drug solanezumab was meant to lower the levels of abeta but was found not to bring recovery or slow the disease progress. We know from research that Alzheimer’s disease starts developing decades before Alzheimer’s dementia is evident. This is because amyloid plaques accumulate years before a person would have detectable symptoms in the brain. Tara says that amyloid plaques kick off a toxic cascade that act as a trigger to Alzheimer’s disease but at some point the disease becomes independent of amyloid changes. What actually causes dementia is cell death that takes place at a later stage down the line. Tara concludes that this is the reason why solanezumab did not work as it may be too late into disease progression.
Drugs that target amyloid may be good as prevention but not as a cure. Amyloid is an important initiating factor for people who already have symptoms but at the time of having memory loss symptoms, a person will have already lost too many neurons and synapses. Tara proposes that there are two streams of therapies – preventative and for people who already have the disease. What our clinical trials in the Centre for Dementia Prevention aim for is to identify people at risk of developing dementia and target a population who don’t have any symptoms but only risk factors.
Tau tangles at a later stage in disease development
Tara says that scientists need to do more work on developing other drugs that target tau. While early in Alzheimer’s disease there are amyloid clumps in the brain cells in the brain, later on in the process tau tangles start accumulating. Normally, tau helps brain cells function normally – in Alzheimer’s disease tau clumps up in the brain cells. Being a neuronal change that takes place at a later stages of the disease, tau is much more associated with disease symptoms. Tara explains that looking at the amount of tau tangles in the brain and how they are spreading predicts dementia symptoms. In conclusion, tau tangles seem to be closer to the cause of cell death than amyloid and therefore a potential target for halting the disease at a stage where memory problems already occur.
Tara suggests that there are two big reasons for a relatively slow progress made in Alzheimer’s disease research. The first one being that brain is incredibly complicated – we don’t understand how the brain works and how we make memories. The second being funding – Tara highlights that we need to spend more money on basic research. The few drugs that have come through research have brought hope but there is a significant amount we don’t know about Alzheimer’s disease itself. Tara make the point that we currently have a funding shortage in Alzheimer’s disease – even though it costs the UK £26 billion per year to care for people living with dementia, we only spend £90 million in research. Comparing dementia funding to cancer and heart disease shows they receive £500 million and £160 million respectively per year from government and charity funding. Tara ends with a positive note reminding that funding research really does make a difference – there have been fantastic new treatments developed for cancer and heart disease that are making a big difference to people’s lives. If we can do same thing in dementia sphere we have a much better chance of curing it.