Can breaking down brain plaques prevent Alzheimer's?
Can breaking down brain plaques prevent Alzheimer's?
Hello everyone,
Many of us may know someone who suffers from dementia or Alzheimer’s disease. Its prevalence and devastating consequences on the patient and their friends and family makes it a top priority for medical research. Despite being described over 100 years ago, this disease still faces limited options for prevention and treatment. It is known that brain plaques correlate with Alzheimer’s disease, and they have been an important focus of research. In order to find out more about the role of these plaques, we asked 21 experts in Alzheimer’s disease, neurodegenerative diseases and medicine, ‘Can breaking down brain plaques prevent Alzheimer’s?’, here is what they said…
EXPERT CONSENSUS
Can breaking down brain plaques prevent Alzheimer's?
18 out of 21 experts say ‘Unlikely’, however new studies are still coming to light
What is Alzheimer’s disease?
Currently, 55 million people worldwide suffer from dementia. 60-70% of these people have Alzheimer’s disease (AD). AD is a progressive condition that begins with mild memory loss and develops into severe amnesia, behavioural changes, and language difficulties.
What are brain plaques and where do they come from?
AD is characterised by an accumulation of protein that forms insoluble brain plaques, which are associated with neuronal cell death and subsequent symptoms.
Dr James Cory-Wright, a medical doctor from the Royal Berkshire Hospital NHS Trust in the UK, says “Brain plaques are a hallmark of Alzheimer’s disease, and the degree of brain plaque correlates with the severity of the disease. However, it is thought that the plaques are an end product of the brain damaging process, and not the cause.”
There are two forms of brain plaques. Dr Donald Royall, an expert in medicine and psychiatry from UT Health San Antonio in the USA, explains that amyloid plaques “are one of the two lesions Alzheimer described. The other is the neurofibrillary tangle (NFT). Both are present in Alzheimer's Disease”
Dr Rebecca Nisbet, an expert in Alzheimer’s disease from Queensland Brain Institute in Australia, says “Amyloid plaques … are formed by the gradual build-up of a toxic protein called amyloid-beta”. These plaques form when this protein misfolds and clumps together, however, it is unclear why this process occurs. It is thought that the soluble intermediates in this process are more toxic to neurons than the insoluble amyloid plaques.
Does breaking down plaques prevent AD?
Out of 21 experts, 18 answered that it is ‘unlikely’ that breaking down plaques could prevent AD.
Dr Nisbet says “Studies in animals have shown that effectively breaking up the amyloid plaques and removing the toxic amyloid-beta from the brain will reduce the disease progression and improve memory. A study from our group demonstrated this using non-invasive scanning ultrasound. Unfortunately, the restoration of memory has not been replicated in human clinical trials yet, despite the successful clearance of amyloid-plaques. However, this may be due to other factors, such as the design of the trials, rather than the treatments themselves.”
Professor Christopher Mitchell, an expert in neurodegenerative disease from Ulster University in Ireland agrees, saying “Certainly, in mouse models there is reasonable evidence to support the hypothesis that preventing plaques forming or breaking them down can prevent AD (at least in the mouse). But as we are aware, what happens in a mouse does not necessarily translate into successful therapy for humans.”
Why might breaking down plaques not help AD?
There are a few reasons why the above studies found that breaking down brain plaques didn’t improve or prevent AD in humans.
One of these may be that plaques form too late in disease progression, when there is already irreversible damage to the brain.
Dr Nisbet says “if amyloid plaques are detected in the brain of an individual presenting with dementia then they likely already have Alzheimer’s disease and breaking up the plaques will not prevent them from getting it.” Dr Louise Serpell, an expert in Alzheimer’s disease from Sussex University in the UK, agrees, saying “Often, amyloid plaques are found in individuals who already have symptoms, so there is no way to reverse these symptoms even if you were able to dissolve the plaques.”
Dr Tim Wilkinson, an expert in neurology and cognitive science from Edinburgh University in Scotland, elaborates, saying “We now think that the plaques and tangles in Alzheimer's disease are present many years (even decades) before a patient develops cognitive symptoms. This is important, because it might explain why we haven't yet found a treatment that works in preventing Alzheimer's disease - maybe, if we wait until someone has symptoms (e.g. memory loss), it is too late for any treatment to work. With this in mind, researchers are trying to find ways of identifying people who are at risk of developing symptoms due to Alzheimer's disease in the future - it is possible that if we were to try these interventions in these people, they may help to prevent or delay the onset of symptoms. This is just a theory though. It is very difficult to do in practice.”
Is there any new evidence around plaques and AD?
Research in AD is ongoing, and new results from clinical trials are still coming to light. We asked these experts about AD a few years ago, however one trial came out at the beginning of this year which showed something quite different. Dr Cory-Wright discusses these new findings, saying “A recent drug trial demonstrated that a monoclonal antibody drug called Lecanemab was able to break down amyloid plaques in patients with established mild Alzheimer’s disease and this slowed progression of the disease. This is the first trial of a plaque targeting monoclonal antibody (MAB) to show a positive outcome.”
Why was this trial successful when previous ones were not? Dr Cory-Wright says “There are several proposed reasons for why this particular trial was successful whereas other similar trials were not. In this trial only people with mild AD were included. It is thought that plaque clearing MABs will not work in patients with more severe disease as extensive and irreversible damage has already taken place. Another reason is that the MAB used in this trial targeted the toxic intermediates as opposed to the plaques themselves, whereas other MABs have targeted the latter. Finally, this trial reduced amyloid levels more effectively and quicker than other trials.”
Despite this success, there are still many questions that remain unanswered. Dr Cory-Wright says “Although amyloid plaque was reduced to a very low level the symptomatic effects were modest during this 18-month trial. This mismatch highlights our lack of understanding of the pathogenesis behind AD. Perhaps there are other processes in AD that are more important than amyloid plaque formation, alternatively, there may be a time-delay for cognitive changes to be seen.”
Does this trial show that we can prevent AD? Dr Cory-Wright says “It is yet to be determined whether giving this MAB to people without established brain plaques could prevent Alzheimer’s disease and, like all drugs, this may come with some risks.”
Dr Cory-Wright concludes “In summary, as breaking down plaques in individuals with mild AD results in some modest delay in memory decline and symptoms, it may well be the case that breaking down plaques in individuals without AD may prevent it altogether - however more research is needed to demonstrate this.”
How else could we prevent AD?
As well as ongoing investigation into amyloid plaques, there is plenty of research which shows that lifestyle factors can influence your risk of developing AD. These include smoking, diabetes, alcohol and not exercising.
Proferssor Mitchell says “There is good epidemiological evidence that maintaining a healthy diet (i.e. specifically not being type 2 diabetic), exercising, perhaps even learning a second language (?) decreases your risk of AD and may help to slow progression of this cruellest of diseases.”
The takeaway:
Historical trials have not found that breaking down amyloid plaques slows progression of AD, however a trial from this 2023 brings new hope to this area of research.
May the facts be with you!
Eva
Is biological ageing inevitable?
Learn more about anti-aging with our deep-diving review.
If you like our newsletters you can make a donation to support our work here at Metafact.
Verified by Metafact is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.