UQ study could guide Alzheimer’s treatment

Researchers from the University of Queensland’s School of Biomedical Sciences have found a crucial link between early brain degeneration, impaired waste clearance in the brain and the deterioration of neurons associated with Alzheimer’s disease.

Professor Elizabeth Coulson, from UQ’s School of Biomedical Science and Queensland Brain Institute, said the findings – published in Nature Communications – have the potential to help explain how Alzheimer’s begins to take hold.

Lead author Associate Professor Kai-Hsiang Chuang added that the research could guide new diagnostics and treatments that target the breakdown of neurons early.

“The five-year study used 25 humans aged 60-90 years, 10 of whom exhibited early mild cognitive impairment, along with animal models,” Dr Chuang said.

“It showed these neurons previously known for cognitive function, also control the blood and fluid movement that drives the cleaning system. Weakening these neurons leads to impaired waste clearance.”

Professor Coulson said the research focused on specific brain neurons that are the first to die in Alzheimer’s disease.

“Our previous studies found the degeneration of these brain neurons and build-up of toxic proteins go hand-in-hand in Alzheimer’s disease,” she said.

“The brain has inbuilt cleaning systems to rid it of waste and toxins, which is essential to cognitive health and preventing neurodegenerative diseases.

“However, how the brain knows to empty the waste is still unclear.’’ 

Another study, led by Dr Ying Xia from UQ’s School of Biomedical Sciences and the CSIRO eHEALTH group, is evaluating the effectiveness of current Alzheimer’s drugs with the aim of determining if they are less effective once neurons are lost, and whether they could change how the disease progresses if treatment is started earlier.

“This will help us understand how to identify the patients who are most likely to benefit from existing treatments,” said Dr Xia.

The findings from Professor Coulson and Dr Chuang’s research also showed commonly prescribed Alzheimer’s drugs partially restored the waste fluid flow but challenged current ideas on when the brain waste disposal system is active.

“Although there has been a lot written about the brain clearing toxins during sleep, this has been debated within the science community,” Professor Coulson said.

“Our studies show the neurons that first die in Alzheimer’s disease are active when we are awake and the brain is active.

“But more research is needed to examine the association between toxin clearance and sleep-wake states.”

The benefit that the current Alzheimer’s treatment drugs, such as choline esterase inhibitors like Aricept, give people – albeit transiently – could be partially through the mechanism the UQ team have uncovered, Professor Coulson told Community Care Review.

“However, this type of drug doesn’t protect the neurons so they continue to degenerate, and  this is why the drug only works for a period of time in most people,” she said.

Professor Coulson has also spent the last 20 years researching whether obstructive sleep apnoea causes neurodegeneration – such as Alzheimer’s disease – discovering the neurotrophin brain receptor p75NTR triggers neuronal death in diseases.

“We are trying to develop a drug to target this p75 cell death receptor to stop the neurons from dying, not just treat the symptoms of dementia,” Professor Coulson said.

“If that worked, it would be a breakthrough and could improve thousands of lives.”

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