Brain research shows how tau toxin helps Alzheimer’s spread

The process by which normal neurons become poisoned by a toxic protein may be the mechanism by which Alzheimer’s disease spreads in its vast majority of victims.

The slow deterioration that comes with age leaves brain cells vulnerable to attack by toxins associated with Alzheimer’s disease.

The process by which normal neurons become poisoned by a toxic protein, then release its “seeds” to colonise other neurons, may be the mechanism by which Alzheimer’s disease spreads in its vast majority of victims: people who have no family history of the condition.

Research by Queensland Brain Institute research fellow Juan Polanco and led by University of Queensland dementia expert Jurgen Gotz has found this can happen in mice and engineered cultured human cells when a normal protein called tau becomes toxic and a neuron’s usual ability to dispose of it is compromised.

“We knew the tiny sacs that encapsulate the tau, exosomes, could induce toxicity, but we didn’t know how they took over the whole cell, or helped the toxicity spread to other cells,” Dr ­Polanco said.

The compromised neuron’s attempt to destroy the toxic tau causes the exosomes to trigger a reaction that punches holes in the neuron’s “stomach”, known as the lysosome. Once the toxic tau has escaped, it begins an irreversible spread into surrounding areas.

As it accumulates in the brain, it forms “tangles” inside neurons, which, together with amyloid plaque, are the key features of ­Alzheimer’s.

“These leaks create a damaging seeding process that causes tau tangles and ultimately lead to memory loss and other impairments,” Professor Gotz said.

The more that is discovered about the mechanisms by which Alzheimer’s and other neuro­degenerative diseases spread, the greater the chance of ultimately devising ways of interfering with the process, Dr Polanco said.

“Along with Alzheimer’s, this cellular process might also play a leading role in other cognitive diseases, from frontal lobe dementia to rare neurological disorders with toxic tau,” Dr Polanco said.

He said there was emerging evidence that exosomes could enable cancerous tumours to metastasise more quickly.

“Improving our understanding of how Alzheimer’s and other diseases spread through exosomes will allow us to create new ways to treat and intervene in these cellular processes,” Dr Polanco said.

Some 400,000-459,000 Australians have dementia, according to Australian Institute of Health and Wellbeing data, with Alzheimer’s disease accounting for up to 70 per cent of diagnosed cases.