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Blood vessel gene linked to both stroke and dementia

11 April 2016
Appeared in BioNews 846

A gene called FOXF2 has been linked to small vessel disease in the brain, a condition associated with a higher risk of stroke and dementia.

Small vessel disease is a major contributor to ischaemic stroke, which is the result of an insufficient oxygen supply to the brain (rather than bleeding into the brain, known as haemorrhagic stroke). It causes more than 80 percent of silent strokes, which have no apparent symptoms but show up on brain scans.

The study draws on data from previous research looking for genes linked to stroke and also suggests that some genes may be associated with both ischaemic and haemorrhagic stroke. Professor Sudha Seshadri, from the Boston University School of Medicine in Massachusetts and a co-author of the study, said that such genes 'may act through a novel pathway affecting pericytes, a type of cell in the wall of small arteries and capillaries'.

The researchers analysed data from 18 other genome-wide association studies. These studies included 84,961 participants of European ancestry, none of whom had had a stroke when recruited. During the follow-up period (ten years, on average), 4348 of them went on to have a stroke. Participants from other ethnic groups were included in subsequent analysis, showing that FOXF2 is a risk gene in all ethnic groups.

Having identified FOXF2 as a risk gene for stroke and dementia in human populations, the researchers studied it in mice and zebrafish to better understand how it is linked to disease. The findings revealed that FOXF2 is involved in the regulation of other genes required for development of blood vessels in the brain.

Blocking FOXF2 led to inflammation and bleeding from small blood vessels in the brain because vessels were weakened from having a lower than normal number of pericytes and smooth muscle cells.

Previous research had already linked small blood-vessel disease to dementia and other neurological disorders, such as gait (walking) problems. The genetic link to stroke is newer because previous stroke research focused on genes that might give rise to ischaemic stroke by causing obstructions, like clots, in the blood flow.

The study was published in The Lancet Neurology. It also confirmed the association of stroke with seven previously discovered genes.

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