New leads on treating dementia and Alzheimer's

May 2, 2018 by Robyn Mills, University of Adelaide
PET scan of a human brain with Alzheimer's disease. Credit: public domain

A new study by scientists in Australia and the US provides an explanation for why clinical trials of drugs targeting proteins in the brain that were thought to cause dementia and Alzheimer's have failed. The study has opened the way for potential new treatments with existing drugs.

Published online in the journal Human Molecular Genetics, the researchers assembled evidence from a wide range of human studies and animal models of -related diseases to show that is a major cause, not just a consequence.

They show that many genes linked with dementia regulate our susceptibility and response to inflammatory damage.

"For decades, scientists have thought that dementia and Alzheimer's Disease are caused by protein aggregates forming in the brain. But recent of drugs that reduce the aggregates have failed," says project leader Professor Robert Richards, from the University of Adelaide's School of Biological Sciences. He is working in collaboration with the University's Adelaide Medical School and the National Institutes of Health, in the US.

Inflammation has long been known to increase as dementia-related diseases progress, but only now is it identified as the cause. Previously it was thought to act simply to clean up caused by the protein aggregates.

"We know that inflammation has different phases – early on it can be protective against a threat by actively degrading it, but if the threat is not removed, then actually causes cell death," says Professor Richards.

The new work turns previous thinking around. The genetic linkages imply that the inflammation comes first – and the tissue damage second.

"Many genes linked with dementia operate at the level of controlling cellular inflammation. Both internal and external triggers interact with these genes to play a part. Inflammation is the point through which many triggers converge," says Professor Richards.

He likens the to a virus infection. "Inflammation is a very effective defence against foreign agents like viruses. But as we get older and accumulate mutations, our cells can make proteins and DNA products that mimic viruses, and these build up in the system," he says.

"Normally, our cells bar-code their own products to tell them apart from foreign agents. When these bar-codes aren't in place, our cells can't properly distinguish 'self' and 'non-self' trigger molecules. The result is inflammation that escalates and spreads – hence the term autoinflammatory disease."

Certain types of gene mutation cause these systems to fail earlier or more often, and can increase as we age – possibly accounting for age-related increased risk of developing dementia. The good news is that by reducing some elements of inflammation, it may be possible to reduce dementia symptoms.

"With this new understanding of the disease, we now need to test existing anti-inflammatory drugs for their effectiveness in treating dementia," he says.

Explore further: Arthritis drugs linked to lower Alzheimer's risk

More information: Robert I Richards et al. Neurodegenerative diseases have genetic hallmarks of autoinflammatory disease, Human Molecular Genetics (2018). DOI: 10.1093/hmg/ddy139

Related Stories

Arthritis drugs linked to lower Alzheimer's risk

February 13, 2018
Scientists from the University of Southampton have teamed up with researchers from the University of Oxford to look at whether existing drugs for arthritis have any effect on a person's risk of developing dementia. By looking ...

Immune system dysfunction may occur early in Alzheimer's disease

February 6, 2018
An association between inflammation biomarkers in both blood plasma and cerebrospinal fluid (CSF) and markers of Alzheimer's disease (AD) associated pathology, has been found by researchers at the University of Colorado Anschutz ...

Finding a treatment for Parkinson's disease dementia

September 2, 2015
University of Adelaide neuroscientists are leading a world-first study into a form of dementia experienced by many Parkinson's disease suffers, which is expected to ultimately lead to a new therapy for the condition.

New study suggests rethink of dementia causes

May 12, 2016
University of Adelaide researchers have developed a new theory for the causes of dementia and other neurodegenerative diseases, involving an out-of-control immune system.

Discovery reveals way to stop inflammation in Alzheimer's, arthritis, more

February 26, 2018
A new discovery about the immune system may allow doctors to treat harmful inflammation that damages the brain in neurodegenerative diseases such as Alzheimer's. It might also let doctors save patients from the potentially ...

Inflammation in midlife linked to brain shrinkage later

November 1, 2017
People who show signs of inflammation in middle age are more likely to suffer from brain shrinkage later in life, a possible precursor to dementia or Alzheimer's disease, researchers said Wednesday.

Recommended for you

What really causes Alzheimer's and how might we fix it?

May 23, 2018
There have been a lot of theories about what causes Alzheimer's disease. Many of them have given rise to experimental treatments of one form or another. None of them have worked much better than taking anything you might ...

Study predicts most people with earliest Alzheimer's signs won't develop dementia associated with the disease

May 22, 2018
During the past decade, researchers have identified new ways to detect the earliest biological signs of Alzheimer's disease. These early signs, which are detected by biomarkers, may be present before a person starts to exhibit ...

Moderate to high intensity exercise does not slow cognitive decline in people with dementia

May 16, 2018
Moderate to high intensity exercise does not slow cognitive (mental) impairment in older people with dementia, finds a trial published by The BMJ today.

Mutation discovered to protect against Alzheimer's disease in mice

May 16, 2018
Researchers at the RIKEN Center for Brain Science have discovered a mutation that can protect against Alzheimer's disease in mice. Published in the scientific journal Nature Communications, the study found that a specific ...

Most deprived are nearly twice as likely to develop dementia

May 16, 2018
Older adults in England with fewer financial resources are more likely to develop dementia, according to new UCL research.

Scientists discover a variation of the genome predisposing to Alzheimer's disease

May 15, 2018
An article published in Nature Medicine shows that the inheritance of small changes in DNA alters the expression of the PM20D1 gene and is associated with an increased risk of developing Alzheimer's disease.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

VOR_
not rated yet May 02, 2018
It's surprising to me that inflammation as causal has not been the leading hypothesis for many years. I seem to have gotten the impression it was, but then I could have assumed that. The article makes it sound like this comes as a surprise. Makes me wonder if that's true and how widespread that surprise is. But what hypothesis would have been more plausible? If this is really a surprise, it seems this is a result of 'empirical bias' where we don't have creative reasoned argument (plausible hypotheses) to go along with observations.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.