Investigating biomarkers for neurodegenerative disease

So in week one, we learned about what the pathologies are in the brains of people with Alzheimer’s disease and other neurodegenerative conditions. But one of the biggest problems we face in this branch of medicine, if you like, is there’s no direct way of measuring those pathologies. We can’t do, we can’t reasonably do, brain biopsies. So what we have to do is use what we call biomarkers to try and approximate, if you like, what’s going on in the brain of individuals at risk or suffering from Alzheimer’s disease. And these biomarkers can come from various places.

So we can look at spinal fluid, which washes around the brain, and picks up the proteins that are present in neurons, and synapses, and supporting cells, called glia and astrocytes. There’s a huge technology development going on at the moment looking at blood tests that might be able to pick up these proteins as well. But perhaps the most developed way of looking at the brain is through neuroimaging.

And this slide, just to my left behind me here, is a typical brain scan of an individual who’d have a diagnosis, probably, of Alzheimer’s dementia So what a neuroradiologist or clinician would look at in the brain scans is the different areas of the brain that may be shrunken or atrophied more than other areas. And if you like, what we’re able to do with the brain scan is look at, if you like, scrolling through from the front of the brain. So those are the eyes one sees.

And if you move to the back, and this is like looking through almost like a slices of a loaf of bread, going backwards through the frontal lobes, going a bit further back in the brain. You can see the ventricles appearing here, the lateral ventricles. And then you move towards the temporal lobes, these two lobes here, as you move further back. You can see the ears beginning to emerge. And what we’re very– this is, obviously, a patient who’s got quite significant atrophy. The ventricles are very large. This fissure here, called the Sylvian fissure, is very wide. And we mentioned earlier, of course, these things called the hippocampal formation. There really shouldn’t be any black here at all.

You should only see a thin line of the gap, if you like, between the hippocampal structure and the medial temporal lobe. So this gives us a lot of information about the structure of the brain. You might see, which isn’t the case here, some evidence of small strokes or problems with blood supply. So the scan that we were looking at a moment ago was somebody who would have had quite advanced Alzheimer’s disease. There was very clear changes in the brain, in terms of the atrophy. But of course, what we’re trying to do in the future, well, now and in the future, is to be able to identify much more subtle earlier changes of neurodegenerative disease many years before symptoms develop.

And imaging techniques, as well as looking at biomarkers in the blood and the CSF, are highly likely to show evidence of change many years before various symptoms of Alzheimer’s disease and other neurodegenerative diseases emerge. And the cohort studies that we’re doing, the follow up of participants in midlife and early old age, are highlighting that there are, indeed, changes in the brain in particular areas, and indeed, in biomarkers many years before one expects dementia to develop. One of the other really exciting things at the moment is that we’ve traditionally looked at brain imaging, or we’ve looked at spinal fluid, or we’ve looked at blood tests.

But of course, there are other things that the brain does which may be affected or, maybe, display evidence of early changes, much, much earlier than, say, for instance, memory testing. And two things that, I think, are particularly exciting is the way we actually speak. The language we use, the complexity of the language we use, how we speak to other people in dialogue, turn taking, how long our pauses are, et cetera, there may be some very subtle changes in the way we speak which are reflective of early neurodegenerative disease. The other area of great interest, at the moment, is actually what’s happening in the back of the eye. The eye is very closely, intimately related to the brain.

And a lot of the pathologies one sees in the brain are also demonstrable in the back of the eye. And of course, looking at the back of the eye is really easy. I mean, every time one go to an optician, the optician will be able to look through a endoscopy and to look into the retina in the back of the eye. But there’s even more advanced photographic and other techniques to look into structures of the back the eye, including nerve cells, blood flow, et cetera. So one imagines that, in the future, these biomarkers to identify early disease could include blood tests, speech, and even being accessed in the high street and the opthamologist.

Really exciting times, we’ve got to understand exactly how these things relate to disease. But I think early detection is going to be much easier in the future than it currently is today.