Scientists may be able to clear brain of Alzheimer's-causing proteins

Scientists may have found way to clear the brain of toxic chemicals responsible for brain diseases like Alzheimer’s and Parkinson’s – but it’s already too late if you’ve got it

• In Alzheimer’s, amyloid beta proteins build up in the brain and clump together
• But researchers say they may have found a way to clear them by ramping up levels of another protein
• In a study on mice genetically-engineered to make more amyloid beta, they found those given compounds that boosted the levels of aquaporin 4 cleared protein faster 
• About 500,000 Americans are diagnosed with Alzheimer’s every year 

A research team may have found a new way to clear harmful proteins in the brain that trigger cognitive diseases like Alzheimer’s and Parkinson’s, opening the door for new treatments for the devastating conditions. 

Experts believe that Alzheimer’s is triggered by amyloid beta proteins building up in the brain and clumping together, triggering tell-tale symptoms such as memory loss and loss of general cognitive function. 

Research from the Washington University School of Medicine in St. Louis, Missouri, found that ramping up levels of a separate protein — aquaporin 4 — could help to remove them.

In a study on mice genetically-engineered to make more amyloid beta, they found that those given compounds that boosted the levels of aquaporin 4 cleared the harmful proteins faster than those that received a placebo or inert liquid.

About 500,000 Americans are diagnosed with Alzheimer’s every year, and 120,000 die from the disease annually. The study suggests that having more aquaporin 4 could help prevent the condition — but not cure it. It is not clear what causes Alzheimer’s disease, however, but some scientists suggest that a build-up of amyloid beta may not be behind it in every case.

Scientists at Washington University School of Medicine in St Louis, Missouri, say they have found that ramping up levels of a protein in the brain could clear other proteins that cause dementia

In the study — published Wednesday in the journal Brain — scientists began by studying how aquaporin 4 was made in the brain.

Every now and again this protein is generated with what they described as a ‘little tail’ on the end.

Initially, the scientists thought this was just a fluke due to an error in how the protein was being generated.

Simple heart scans may be able to predict your risk of being diagnosed dementia within a decade, a study suggests.

Researchers found elderly people with abnormalities in their left atrium were a third more likely to develop the disease — even if they showed no sign of heart problems.

It suggests scans normally only used for people with suspected heart disease or heart attack patients could help identify who is at highest risk of dementia.

The left atrium helps pump oxygenated blood to vital organs, including the brain. If the chamber is faulty, it can reduce blood flow to the brain — a risk for dementia.

Atrial cardiopathy is the term for a variety of conditions that can cause the left atrium not to work properly.

It can lead to strokes and an irregular heartbeat, two complications that have also been linked with dementia.

But the study of more than 5,000 American adults in their 70s concluded atrial cardiopathy was an ‘independent risk factor’.

The researchers, led by Johns Hopkins University in Baltimore, said it could help inform ‘new interventional strategies’.

But research quickly revealed that genes coding for this change were in several different species.  

Testing showed that it was also normally around support cells — called astrocytes — which are near blood vessels. They said this was the ‘perfect place’ to be if it was used to flush out unwanted substances — such as amyloid beta.

To test the theory, they boosted the levels of aquaporin 4 in mice that had been genetically engineered to make more amyloid beta.

Dr. Darshan Sapkota, the biologist who led the study, screened 2,560 compounds to work out which might be able to ramp up the production.

He found two that could help: Apigenin — normally found in chamomile, parsley, onions and other plants — and sulphaquinoxaline — an antibiotic used by vets.

In the study, mice were then administered with either apigenin, sulphaquinoxaline, or a placebo.

Results showed those that got the compounds cleared amyloid beta faster than those that did not. 

It was not clear how the substances were administered to mice, whether via supplements or through injections. 

The scientists said it was not safe for people to consume the antibiotic sulphaquinoxaline without a prescription.

Although apigenin is available as a dietary supplement, they also cautioned against consuming large amounts of it because it is not known how much gets to the brain.

The scientists are now looking for new compounds that would influence the production of aquaporin 4 to take to further trials — and eventually human trials if they are shown to be safe.

But scientists are not clear on what causes Alzheimer’s — which affects about six million Americans.

The build up of amyloid beta in the brain is the prevailing hypothesis, because the plaques harm communication between cells. But some papers suggest that — while this is associated with the condition — it may not actually cause it.

A study from the University of California, San Diego, published in 2020 on 700 people is among those to suggest amyloid beta was associated with the condition in some cases rather than the root cause.

Dr. John Cirrito, a neurologist also involved in the study, said: ‘There’s lots of data that says reducing amyloid levels by just 20 percent to 25 percent stops amyloid build-up, at least in mice, and the effects we saw were in that ballpark.

‘That tells me that this could be a novel approach to treating Alzheimer’s and other neurodegenerative diseases that involve protein aggregation in the brain. 

‘There’s nothing that says this process is specific for amyloid beta. It may be enhancing, say, alpha-synuclein clearance, too which could benefit people with Parkinson’s disease.’

The team is now working on uncovering drugs that would influence the production of aquaporin 4 by looking at sulphaquinoxaline and other compounds.

Sapkota added: ‘We’re looking for something that could be quickly translated into the clinic.

‘Just knowing that it’s targetable at all by a drug is a helpful hint that there’s going to be something out there we can use.’

The research was part funded by the National Institute of Neurological Disorders and Strokes.

Sapkota led the study while a post-doc at Washington University but is now an assistant professor in biological sciences at the University of Texas, Dallas.

Alzheimer’s disease is the most common form of dementia that currently affects about six million Americans.

It is thought to be caused by the abnormal build-up of proteins in and around brain cells, including amyloid beta. Others involved are known as tau.

Scientists are not sure why these build up in some people, but it could be linked to genetic factors, diet or a head injury — among others.

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