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AAIC 2021 | Endothelial biomarkers for vascular contributions to dementia

Atticus Hainsworth, PhD, St. George’s University of London, describes the endothelium and its role in the brain, explaining that endothelial dysfunction may contribute to dementia pathology. The endothelium has also recently emerged as a potential source of biomarkers. Dr Hainsworth explains the role of biomarkers in identifying where intervention is required in disease and highlights the work of the MarkVCID consortium in identifying placental growth factor, which shows great potential as a biomarker for vascular contributions to cognitive impairment and dementia (VCID). He concludes by discussing the recent surge in biomarkers being identified, as well as explaining their value in assessing the efficacy of potential treatments. This interview took place during the Alzheimer’s Association International Conference (AAIC), 2021.

Transcript (edited for clarity)

That was coming from a lot of work I’ve done in collaboration with many friends and colleagues in the UK and overseas as well, on the endothelium. Just to back up, the endothelium means the cells that line all our blood vessels, every blood vessel in the body, but the ones in the brain have a particular sort of profile and a specific job, as you can imagine. The brain has needs that are different from other organs like the liver and the kidneys and so on...

That was coming from a lot of work I’ve done in collaboration with many friends and colleagues in the UK and overseas as well, on the endothelium. Just to back up, the endothelium means the cells that line all our blood vessels, every blood vessel in the body, but the ones in the brain have a particular sort of profile and a specific job, as you can imagine. The brain has needs that are different from other organs like the liver and the kidneys and so on. So the endothelial cells help to give the brain what it needs and they probably play a part in the sort of vascular pathologies I’ve been talking about that contribute to late-life dementia. And they may also, in recent years, they emerged as a possible source of what are called biomarkers, which are molecules or features that give us a sort of read out on how the pathology process is going.

If the biomarker says, well it’s high, it’s severe, then we assume this is a person who needs some aggressive intervention. If the biomarker is low and at very normal physiological levels, we might say, “Well, that’s fine. We don’t need to intervene. There’s nothing to treat here.” So they’ve yielded some really interesting biomarkers. One that struck me at the meeting was the placental growth factor that Donna Wilcock from Kentucky reported, and that’s come out of a big American trial called MarkVCID. It’s a protein, a peptide. It comes from endothelial cells among others. And it really does look quite promising as a biomarker that could be a relevant one for dementia, particularly vascular contributions to dementia.

There’s an impressive blossoming of biomarkers. I think probably naturally enough, not all of them will turn out to be good, but I think it’s encouraging there are so many. We clearly need them. We’re going to need them for diagnosis, for better triaging of patients, for working out who’s best treated in a certain way. And also as markers that tell us how well a treatment is doing. That’s something I think we can really benefit from, having a readout that says you’ve engaged with the molecular target and the disease process is being damped down. That’ll be useful in clinical trials, and it’ll also be useful when we get some therapies in rolling them out to general use.

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Disclosures

Atticus H Hainsworth has received honoraria from Eli-Lilly and from NIA, he chairs the Vascular Cognitive Disorders professional interest area within ISTAART and he leads the MRC-Dementias Platform UK (DPUK) Vascular Experimental Medicine group.