New study identifies probable cause of Alzheimer’s disease

Groundbreaking new research led by Curtin University has uncovered a probable cause of Alzheimer’s disease, in an important finding that offers potential new opportunities for prevention and treatment for Australia’s second leading cause of death.

The study, published in the prestigious PLOS Biology journal and tested in mouse models, identified that a probable cause of Alzheimer’s disease was the leakage of blood into the brain of fat-carrying particles carrying toxic proteins.

Professor John Mamo, principal investigator at Curtin Health Innovation Research Institute (CHIRI), said his collaborative group of Australian scientists had identified the likely ‘blood-to-brain pathway’ that can lead to Alzheimer’s disease, the form of most prevalent dementia in the world.

“While we previously knew that the main hallmark of people living with Alzheimer’s disease was the gradual build-up of toxic protein deposits in the brain called beta-amyloid, researchers did not know where the amyloid came from or why it was deposited in the brain ”. said Professor Mamo.

“Our research shows that these toxic protein deposits that form in the brains of people with Alzheimer’s disease most likely infiltrate the brain from particles that carry fat in the blood, called lipoproteins.

“This ‘blood-to-brain pathway’ is important because if we can manage the blood levels of amyloid lipoproteins and prevent their leakage into the brain, it opens up potential new treatments to prevent Alzheimer’s disease and slow memory loss. “

Building on previous award-winning research which has shown that beta-amyloid is made outside the brain with lipoproteins, Prof. Mamo’s team tested the revolutionary ‘blood-to-brain pathway’ by genetically manipulating models of mice to produce only amyloid human liver which makes lipoproteins.

“As we predicted, the study found that mouse models producing lipoprotein-amyloid in the liver suffered from inflammation in the brain, accelerated brain cell death, and memory loss,” said Professor Mamo.

“Although more studies are now needed, this finding shows that the abundance of these toxic protein deposits in the blood could potentially be treated through a person’s diet and certain drugs that could specifically target amyloid lipoproteins,” thus reducing their risk or slowing the progression of Alzheimer’s disease. . “

Alzheimer WA deputy chairman Professor Warren Harding said the findings could have a significant global impact for the millions of people living with Alzheimer’s disease.

“It is important that universities like Curtin work with the pharmaceutical industry if we are to fight this devastating disease,” said Harding.

“In Australia, around 250 people are diagnosed with dementia every day, adding to the staggering half a million Australians already living with dementia. Without significant medical advances like the breakthrough achieved by the Professor Mamo’s team, it is estimated that the number of Australians living with dementia will exceed one million by 2058. This has a significant impact on families, caregivers and communities.

Previous research by Professor Mamo and his research team in this area received the NHMRC-Marshall and Warren Award for Most Innovative and Potentially Transformative Research.

Currently, the team is conducting a clinical trial, the Probucol in Alzheimer’s clinical trial, based on previous findings that a historical cardiovascular agent reduces lipoprotein-amyloid production and supports cognitive performance in mice.

The full article is titled “Liver proteins can cause Alzheimer’s disease in the brain”.