Patients with Alzheimer’s could have their memory improved by unblocking blood vessels in the brain, scientists believe.
Alzheimer’s is known to reduce blood flow to the brain and research has now found this could be caused by white blood cells sticking to the inside of blood vessels.
And, in a study on mice, memory and brain performance were quickly improved when scientists removed these blockages.
It could be a ‘game-changer’ if the same mechanism can be applied to the millions of people suffering with the disease worldwide, experts say.
Patients with Alzheimer’s could have their memory improved by unblocking blood vessels in the brain, scientists hope on the back of a mice model study
The researchers stumbled across the finding by accident, when Nozomi Nishimura, an associate professor in the Meinig School, Cornell University, was attempting to put clots in the blood vessels of Alzheimer’s mouse brains to see their effect.
‘It turns out that … the blockages we were trying to induce were already in there,’ she said.
‘It sort of turned the research around – this is a phenomenon that was already happening.’
Professor Nishimura worked with Professor Chris Schaffer over the next decade to find that only about two per cent of brain capillaries had these blockages or ‘stalls’.
But the cumulative effect of that small number of stalls was an approximately 20 per cent overall decrease in brain blood flow, due to the slowing of downstream vessels by the capillaries that were stalled.
Recent studies suggest that brain blood flow deficits are one of the earliest detectable symptoms of dementia, suggesting this could also be useful for diagnosis.
To test their theory that it was white blood cells stuck to the inside of capillaries, the smallest blood vessels in the brain, the team ‘unblocked’ the vessels.
They gave an antibody to the mice with Alzheimer’s which interfered with the adhesion of white blood cells to the capilary walls.
WHAT IS ALZHEIMER’S DISEASE?
Alzheimer’s disease is a progressive, degenerative disease of the brain, in which build-up of abnormal proteins causes nerve cells to die.
This disrupts the transmitters that carry messages, and causes the brain to shrink.
More than 5 million people suffer from the disease in the US, where it is the 6th leading cause of death.
As brain cells die, the functions they provide are lost.
That includes memory, orientation and the ability to think and reason.
The progress of the disease is slow and gradual.
On average, patients live five to seven years after diagnosis, but some may live for ten to 15 years.
- Loss of short-term memory
- Behavioral changes
- Mood swings
- Difficulties dealing with money or making a phone call
- Severe memory loss, forgetting close family members, familiar objects or places
- Becoming anxious and frustrated over inability to make sense of the world, leading to aggressive behavior
- Eventually lose ability to walk
- May have problems eating
- The majority will eventually need 24-hour care
Source: Alzheimer’s Association
This increased the blood flow to the brain, the findings, published in Nature Neuroscience, said.
This improved memory function within a few hours, even in aged mice with more advanced stages of Alzheimer’s disease.
Although it worked in mice, the team are yet to figure out if it could work with humans.
An antibody couldn’t be used in humans, and interfering with white blood cell adhesion would affect an individuals immune system.
‘What we’ve done is identify the cellular mechanism that causes reduced brain blood flow in Alzheimer’s disease models, which is neutrophils [white blood cells] sticking in capillaries,’ Professor Schaffer said.
‘We’ve shown that when we block the cellular mechanism [that causes the stalls], we get an improved blood flow, and associated with that improved blood flow is immediate restoration of cognitive performance of spatial- and working-memory tasks.
‘Now that we know the cellular mechanism, it’s a much narrower path to identify the drug or the therapeutic approach to treat it.’
Approximately 20 drugs, many of them already FDA approved for human use, have been identified as having potential in dementia therapy.
Some of them, however, were designed to be taken in high doses for short periods of time to treat sepsis, or in the immediate aftermath of a heart attack or stroke.
Although they aren’t ideal to take long-term, Professor Schaffer said they are still testing these drugs in Alzheimer’s mice now.
Professor Schaffer said he’s ‘super-optimistic’ that, if the same capillary-blocking mechanism is at play in humans as it is in mice, this line of research ‘could be a complete game-changer for people with Alzheimer’s disease’.
Alzheimer’s disease is thought to be caused by the abnormal build-up of proteins in and around brain cells.
Research has shown that many people with Alzheimer’s have blood vessel damage in their brains as well, leading to the belief that this damage to blood vessels may affect the progression of the disease at its very early stages.
Research has found that a reduction in blood flow prevents brain cells from receiving the oxygen and nutrients they need, possibly impairing memory further.
Alzheimer’s disease is the most common type of dementia, affecting 62 per cent of the 850,000 people diagnosed in the UK.