New study reveals how blood vessel cells shape dementia risk
by Eliza Kania
A new study has revealed that the cells lining our brain鈥檚 blood vessels play a more significant role in dementia than previously understood.
In 2024, it was estimated that approximately 982,000 people were living with dementia in the United Kingdom – a figure projected to rise to 1.4 million by 2040 [1]. Understanding the biological mechanisms driving this challenging condition has never been more urgent.
The study led by 性视界 London PhD students Kevin Chris Ziegler and Aydan Askarova has revealed that the cells lining our brain’s blood vessels play a far more significant role in dementia than previously understood.
“Many patients with Alzheimer’s disease also have vascular changes linked to small vessel disease, and roughly 20% of all dementia cases are classified as vascular dementia,” said Kevin Chris Ziegler, co-lead author and PhD researcher at the UK Dementia Research Institute at Imperial.
, is co-authored by from the Department of Brain Sciences and UKDRI at Imperial.
The importance of vascular cells
“These studies will provide information on how to modulate genes associated with dementia risk,” said Dr Nott. To uncover how genetic risk for dementia develops at the cellular level, the research team began by mapping active gene regulatory regions across six brain cell types – from both young individuals (aged 4–19) and older adults (aged 75–87). They identified which genes were active in each cell type by detecting chemical markers that show whether DNA regions are switched on or off.
Next, the team created detailed maps showing how different parts of DNA communicate with each other. This revealed how regulatory switches control genes, even when they're located far apart. The researchers then combined these maps with genetic data from over one million individuals.
This allowed them to identify which brain cell types are most strongly linked to genetic susceptibility to dementia. Using computational tools, they connected genetic variants to their target genes within specific cell types – going well beyond previous approaches that could only identify broad regions of interest.
“We have uncovered important differences in how genes and their regulation contribute to the genetic risk of Alzheimer’s disease and cerebral small vessel disease,” said Dr Alexi Nott. The analysis showed that small vessel disease risk genes were linked to cellular senescence, DNA damage responses, and chromatin regulation – pointing to fundamentally distinct disease mechanisms despite overlapping clinical features.
“The interface where vascular and immune cells interact appears to be a hotspot for genetic risk,” explained Mr Ziegler. “Our work identifies genes dysregulated by risk-associated enhancers, offering new avenues for developing potential treatments,” he added.
Future treatments and impacts
The implications of this research extend beyond the lab. As researchers emphasised, understanding how Alzheimer’s disease and cerebral small vessel disease interact could lead to better prevention and treatment. The breakdown of the blood-brain barrier and reduced cerebral blood flow seen in early Alzheimer’s disease may result from genetic vulnerability in endothelial cells and pericytes – the cells that maintain vessel integrity.
“This work helps deepen our understanding of how Alzheimer's and cerebral small vessel disease (SVD) develop and interact, paving the way toward better ways to prevent or treat dementia more broadly,” Dr Nott summarised.
Globally, dementia affects over 55 million people, and this number is projected to reach 139 million by 2050[2]. Alzheimer’s disease, the most common form of dementia, causes progressive memory loss, confusion, language difficulties, and changes in mood and behaviour – eventually leading to loss of independence and the need for full-time care.
According to the latest Alzheimer’s Society report, 42% of people with dementia reported feeling ashamed or stigmatised by their symptoms. The condition also impacts those closest to them: 70% of unpaid carers report that their mental or physical health has been negatively affected, spending less time on activities they enjoy or feeling more socially isolated.[3]
Additionally, it is estimated that around 70% of care home residents have dementia. Both conditions impose not only substantial personal but also economic costs. Dementia cost the UK £42.5 billion in 2024 – 77% of which was linked to social care.[4]
The research was supported by the UK Dementia Research Institute and the Alzheimer’s Association. It represents a major step forward in understanding the cellular and genetic complexity of dementia, offering hope for more precise, personalised approaches to prevention and treatment in the future.
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Reporter
Eliza Kania
Faculty of Medicine Centre