Beyond brain cells in neurodegeneration


By Mardi Chapman

5 Dec 2018

Neurones aren’t the be-all and end-all in neurodegenerative disease – and neither is the brain, the Australasian Neuroscience Society 2018 conference was told.

Delivering the inaugural Elspeth McLachlan Plenary Lecture, Professor Glenda Halliday said peripheral blood cells such as monocytes and even the gut microbiome were integral to the process of neurodegeneration.

She told the limbic the brain was involved much earlier than the presentation of clinical symptoms.

“And there is actually quite a number of different cells that are involved to get the degeneration, and they are not necessarily in the brain,” she said.

“There is actually an integrated suite of immune changes that have to happen to result in degeneration in the brain.”

Professor Halliday, a member of the Brain and Mind Centre at the University of Sydney, told the meeting that peripheral blood cells were certainly more convenient to study than neurones.

Recent work by her group has identified monocyte glucocerebrosiderase activity is reduced in patients with Parkinson’s disease compared to controls.

The study found plasma levels of the lipid ceramide were highly correlated with glucocerebrosiderase activity and therefore also decreased in patients with Parkinson’s disease.

The bonus was that therapeutics already available for the management of the lysosomal storage disorder Gaucher disease, which shared mutations in the glucocerebrosidase gene, may have a future role in Parkinson’s disease.

Professor Halliday said a range of experimental studies had shown evidence for direct or indirect communication between gut bacteria and the brain and that it could be manipulated.

“The microbiome obviously has an impact on nearly every type of tissue. So whatever is happening in other tissues is also happening in the brain with the microbiome interacting with immune responses.”

“I think there will be interventions, which I don’t think we can envisage at the moment, which will be specific for each of the different [neurodegenerative] diseases.”

Professor Halliday referenced research from earlier this year, which demonstrated that innate immune memory in the brain shapes the hallmarks of neurological disease.

The research, published in Nature, highlights the important role of the microglia and the possibility that long-term modulation of microglial responses to peripheral immune stimulation may contribute to the severity of many neurological diseases.

Other interesting research from this year, conducted in a model of MS, suggested the contribution of microglia and astrocytes to neurodegeneration could be mediated by microbial metabolites.

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