Alzheimer’s may be triggered by capillaries in the brain being ‘squeezed’, research suggests.
Poor blood flow through the vital organ is often an early warning sign someone is suffering from the memory-robbing disorder.
And now scientists have discovered amyloid β protein, which causes the tell-tale plaques in an Alzheimer’s patient’s brain, constricts blood vessels.
This constriction could half the brain’s blood supply, depriving its cells of oxygen and vital nutrients.
Researchers hope a drug that blocks amyloid β’s ability to constrict capillaries could prevent cognitive decline in Alzheimer’s patients.
However, other experts warn ‘a cure or effective treatment is still a very long way off’.
Alzheimer’s may be triggered by ‘squeezed’ capillaries in the brain (stock)
The research was carried out at University College London and led by Dr Ross Nortley, of the department of neuroscience, physiology and pharmacology.
‘Our study has, for the first time, identified the underlying mechanism behind the reduction of brain blood flow in Alzheimer’s disease,’ Dr Nortley said.
‘Since reduced blood flow is the first clinically detectable sign of Alzheimer’s, our research generates new leads for possible treatments in the early phase of the disease.’
Dementia affects 850,000 people in the UK, of which 62 per cent have Alzheimer’s, according to the Alzheimer’s Society.
And in the US, 5.8million people are living with the incurable condition, which is set to rise to nearly 14million by 2050, Alzheimer’s Association statistics show.
Blood flow to the brain can be reduced by more than 40 per cent in Alzheimer’s sufferers, the researchers wrote in the journal Science.
While it has long been known patients have constricted capillaries in their vital organ, research into this was neglected as scientists focused on how amyloid β damages neurones, they add.
Vascular resistance largely occurs in the brain’s capillaries. This describes the resistance blood must overcome to flow through the circulatory system.
This is controlled by brain cells called pericytes, which past studies suggest may be ‘out of sync’ in dementia sufferers.
To uncover more about how this occurs, the researchers looked at ‘slices’ of brain tissue that were collected from 13 living humans during neurosurgery.
They then analysed how the tissue’s pericytes reacted to long term amyloid β exposure.
Results revealed exposing the samples to amyloid β reduced the diameter of the tissues’ capillaries by around 25 per cent after 40 minutes.
Constriction peaked at 30 per cent at pericytes, which could reduce blood flow by around half, the researchers claim.
Due to a limited availability of human brain tissue samples, the scientists also analysed four mice that were genetically engineered to have Alzheimer’s and three rodents without the disease.
Of the 20 rat capillaries analysed, 16 had more than a five per cent constriction in response to amyloid β, which was most profound at pericytes.
This is thought to occur due to amyloid β leading to the production of reactive oxygen species (ROS).
ROS are molecules that contain oxygen and react easily with other molecules in a cell.
This then leads to the release of the vasoconstrictor endothelin-1, which activates receptors on pericytes.
Once capillaries in the brain have been constricted, they appear to stimulate the production of amyloid β in a feedback loop.
Study author Professor David Attwell added: ‘Our research raises the question of what fraction of the damage [in Alzheimer’s] is a consequence of the decrease in energy supply that amyloid produces by constricting the brain’s finer blood vessels.
‘In clinical trials, drugs that clear amyloid beta from the brain have not succeeded in slowing mental decline at a relatively late phase of the disease.
‘We now have a new avenue for therapies intervening at an earlier stage.’
However, studies must first uncover why some elderly people accumulate amyloid β without developing Alzheimer’s, the researchers claim.
These pensioners may compensate for vasoconstriction by activating ‘dilatory mechanisms’, they add.
Other experts are also hesitant to suggest this could lead to a cure.
Paul Edwards, director of clinical services at Dementia UK, told MailOnline: ‘The more we know about the causes and effects of dementia, the better.
‘But a cure or effective treatment is still a very long way off.
‘Until that time, the best preventative measures are to live well and healthily, exercising regularly and keeping socially active.
‘And the most important thing for people showing signs of cognitive impairment is timely diagnosis and follow-up support’.