LATE dementia discovered

It’s been described by some as one of the biggest dementia breakthroughs in the last decade. Scientists have categorised a new form of the condition. Katie Haylor spoke with cognitive neuroscientist Duncan Astle from  Cambridge University, who's been purusing the paper...

Duncan - To give it its long title: Limbic predominant age related TPD 43 Encephalopathy or LATE for short.

Katie - It's not the catchiest.

Duncan - No but it's got the good acronym - LATE. When I say new, I'm not suggesting this is something new that has just started occurring, it's been occurring for a long time. It's new in the sense that we have been able to identify it and classify it and separate it out from other forms of dementia. So, in this paper they studied the brains of individuals post-mortem from people who have donated their brains, and they found about 25 percent of their sample had a build-up of a particular type of protein which is called TPD 23 protein. And it is in the limbic areas, that's areas of the brain like the hippocampus which we know is really important for memory and amygdala which is really important for emotional processing. The symptoms include things like memory loss and they're very similar to the symptoms of Alzheimer's disease, but really crucially the underlying cause is different.

So, Alzheimer's disease is driven by a build-up of different types of protein like amyloid B plaque proteins and tau proteins. And they’re sort of tangly proteins that build up inside cells in the brain to the point that they impair the cells functioning and ultimately, they die. So that's one particular cause and that gives rise to Alzheimer's, but these are different proteins and they give rise to this new late form of dementia.

Katie - This is very interesting but what is the relevance of understanding that this is a different type of dementia?

Duncan - Treatments for dementia are few and far between at the minute, and it's been incredibly difficult to develop new drugs that will translate to a kind of prescription that you could be given by your GP. So pharmaceutical companies have been very good at finding compounds that work in the test tube or in an animal model of the disease, but when you get to what's called Phase 1 randomized controlled trial, that's the first point at which that compound will come into contact with human subjects. The vast majority of those compounds fail.

Now one potential crucial reason why they might not work in practice is because when we identify the patients that we want to try the new drug out on, what we're doing is accidentally including lots of patients who have superficially similar symptoms, but a very different underlying pathology. So, for instance, let's say we gather a group of subjects for our new drug and we think they've all the Alzheimer’s and a good proportion of them do, but let's say a third of them actually have LATE. Now there's no reason that your drug would be effective with them because they don't have the same pathology.

Now when you run your trial, of course, your medication only stands a chance of working in a reduced proportion of your sample. And so, the overall efficacy of the drug will always look like it's reduced by comparison than relative to what is required for a trial. And so, the very process of being able to demarcate out different types of dementia with different types of underlying pathology is crucial. The experts in dementia said this is one of the biggest breakthroughs in dementia for the last decade. And that's because until we can understand the different pathways to having dementia we don't really stand a chance of developing proper treatments for it.

Katie - Do we know how many people may have this LATE form of dementia compared to people who might have Alzheimer’s?

Duncan – Not as yet and that's because the next step, having identified that it exists and what the underlying cause is, is to find ways of producing what's called biomarkers. So that's a way of you knowing whether or not a person has a particular specific disorder relative to say Alzheimer’s. And so that requires lots more work in test tubes and in animal models and hopefully, ultimately, with new imaging so that we can do it with human subjects.

Katie - Oh I see. Because crucially this is whilst they're alive rather than post-mortem when they’ve died?

Duncan – Exactly. So, to be able to distinguish them from our Alzheimer’s patients to kind of tease them out for the purpose of doing Alzheimer's trials, but then also to study their condition as well and identify treatments requires that we have ways of detecting it in people who are alive so that we can trial treatments on them. And that's the next step.