When people are diagnosed with Alzheimer’s disease, dementia appears to hover like a sword of Damocles over their head. It seems as though it is simply part of getting older, but that does not have to be the case, international Alzheimer’s expert Bart De Strooper says. The disease is revealing more and more of its secrets. We are all growing older healthier and new medications are constantly being developed, so there are many reasons to be optimistic.
At the beginning of the 20th century, German doctor Aloïs Alzheimer was the first to describe a number of the typical characteristics in the brains of Alzheimer patients. When the doctor conducted an autopsy of a patient’s brain, he discovered that there were important changes in brain tissue. He found strange protein accumulations – plaques – around the braincells and fibrous clusters in the cells.
Researchers later discovered that the plaques and clusters lead to the death of the brain cells. In the early stage, symptoms include problems with memory, speech, and language. Gradually, patients begin to lose their sense of orientation, they become demotivated, and take less initiative. As time progresses, it becomes difficult for them to live independently and they begin to suffer from psychological problems and behavioural disturbances. And in the final stage of the disease, dementia occurs.
Plaques versus clusters
These plaques and clusters led to a scientific debate that raged for decades, neuroscientist Bart De Strooper says. “Which should we focus on in our search for a treatment?” De Strooper leads the VIB-KU Leuven Centre for Brain Research and is also half-time director of the Dementia Research Institute in London. Over the course of his distinguished career, he has seen our knowledge about Alzheimer’s evolve.
“We now understand the molecular structure of Alzheimer’s quite well. We know that the plaques are clots of the protein amyloid beta; the clusters are formed by a different protein called tau. The plaques inhibit the proper functioning of the cells and lead to clusters of tau building up in the cells. In other words, the process starts with amyloid beta, and so that should be our target.”
Significant advances have recently also been made with respect to the genetic background of Alzheimer’s. De Strooper himself made his name thanks to his research into the hereditary type of Alzheimer’s. In 1998, he published a study in the scientific journal Nature that for the first time demonstrated that the problem lay with presenilins, the ‘little scissors’ that are supposed to cut the protein in our brains. If that does not happen the right way, amyloid beta proteins start sticking together and forming plaques.
The hereditary form of the disease is very rare. It is caused by a specific genetic mutation and usually starts at a young age, sometimes even as young as thirty or forty years old. But the majority of types of Alzheimer’s are caused by a combination of ageing, a series of high-risk genes, and environmental factors. Dozens of different kinds of genes have been analysed that increase the risk of dementia in old age. Being a carrier of such a high-risk gene does not mean that you will suffer from the disease – which is the case for the hereditary variant –, just that there is a higher risk. This is why Alzheimer’s occurs more frequently in some families but not all family members will suffer from the disease.
Why does one carrier of high-risk genes develop the disease while another does not? Environmental factors that are primarily related to our lifestyles play a big role here. The older you become, the more likely you are to develop Alzheimer’s. But that risk increases if you are not highly educated or suffer from obesity, diabetes, high blood pressure, lack of exercise, social isolation, depression, hearing loss, or are a smoker. “The basic point is that we have to do everything we can to grow older in a healthier way: eat healthily, get more exercise, wear a hearing aid, etc. But that is true in any case, not only to prevent Alzheimer’s The good news is that this does appear to be happening and we are growing older healthier. That explains why Alzheimer’s is occurring at increasingly older ages.”
The medications that have hitherto been used to combat Alzheimer’s only treat the symptoms. In the search for a better treatment, scientists have been attempting for years to develop medications that remove the plaques and clusters. There is tentative good news in this area. The American pharmaceutical company Biogen and its Japanese counterpart Eisai announced at the end of 2019 that they have found a method of slowing down the memory degeneration of Alzheimer patients. “It is called aducanumab, a medication that attaches to the protein amyloid beta so that the immune system can identify the clots and remove them. Dementia appears to stabilize when patients receive high doses over longer periods of time.” The pharmaceutical companies have applied to the FDA, the American institute that approves new medications. So it is a question of waiting to see whether this first new treatment for Alzheimer’s will be given the green light.
The good news about medication does not mean that the search will be called off. “There are people with plaques in their brain who never develop dementia. The question is why.” Based on De Strooper’s recent research, it appears that this is related to the immune cells in our brain. These are called microglia, and might be described as the Pacman of the brain. They are specialized immune cells that remove foreign and other threatening substances by eating them.
In the case of Alzheimer’s, the microglia clean up both the protein clots and infected and dead brain cells. But the microglia do not work as effectively in carriers of high-risk genes for Alzheimer’s. “We used to search for the origins of the plaques, but now we study the reactions of brain cells around these plaques. Like so many things in life, it is not about what happens, but how you deal with it.” If you have good genes, your microglia will simply clean up the plaques and you will not have Alzheimer’s. “For the people with bad genes, we have to find a treatment that is effective at a very early stage of the disease – before the microglia have any problems. That is the focus of our research with stem cells and new imaging technology.”
We will never develop a medication to cure dementia, but we can develop a medication to prevent it
De Strooper says it is important that the taboo around dementia disappears: “Dementia is a symptom in the final stage of Alzheimer’s – as well as of a number of other brain conditions – but the first changes in the brain start happening twenty years earlier. One serious problem is that the diagnosis of Alzheimer’s often comes too late, when treatment is usually impossible. This means that when it comes to Alzheimer’s, we must diagnose and treat much earlier. That is why it is important to talk about it and diagnose it in time. And I see that happening more and more, in the same way that cancer is now no longer taboo. That is a good thing because we will never develop a medication to cure dementia, but we can develop a medication to prevent it.”