An exotic fish commonly kept in household aquariums may hold the key to treating Alzheimer’s disease, according to new research.
The humble zebrafish has a similarly complex brain to a human – and can replace lost neurons, say scientists.
Small and stripy, the tropical species is native to the streams of the southern Himalayas.
And, unlike us, it has remarkable regenerative capacities. If brain cells are destroyed by illness or injury, they will easily regrow from ‘progenitor cells’.
These have the ability to transform themselves into other types of cell depending on where they are placed in the body.
Now, the team has discovered how this is done in fish exposed to amyloid beta – the rogue protein that causes Alzheimer’s.
Study leader Dr Caghan Kizil, of the German Centre for Neurodegenerative Diseases, said: “Much of Alzheimer research has focused on trying to prevent neurons from dying.
“We see an alternative approach in attempting to induce the regeneration of lost cells.”
Using sophisticated techniques, they analysed the process in great detail for the first time and idenitifed eight specific types of cell.
Interestingly, in the zebrafish model of amyloid build up only some increased in numbers to restore lost cells.
In Alzheimer’s the protein clumps together, killing neurons and leading to the devastating symptoms of memory loss and confusion.
Characterising the molecular basis of progenitor cells proliferative abilities could lead to the development of drugs that target them.
The study, published in the journal Cell Reports, marks a fresh method in combating dementia which affects around 850,000 people in the UK alone, a figure that will rise to 2 million by 2050.
It is a challenging task, since the regenerative properties of the human brain is rather limited.
There are some stem cells in adult grey matter that produce new neurons. But they only reside in two restricted regions and give rise to merely a small variety.
Zebrafish, on the other hand, can readily regrow lost brain tissue.
Dr Kizil said: “Zebrafish and mammals are related in evolution. We therefore think regenerative capacities in mammals are subliminally present and evocable.
“We can learn from investigating the molecular pathways and cellular interactions in zebrafish and harness this knowledge to better understand how regeneration can be boosted in mice and eventually in humans.”
His team used a state of the art system called “single cell sequencing” that examines the genomes of individual cells by providing high-resolution images of each one. It was previously unknown that there are at least eight different kinds.
When they challenged the brain with amyloid-beta found in Alzheimer’s patients, some – but not all – spread and produced new cells.
Moreover, the researchers elucidated how the molecular programs of each cell population changes in response to the toxic protein.
The data can now be used to identify candidate genes that trigger regeneration in the fish model of amyloid accumulation, they explained.
As a proof of principle, the team singled out one such candidate, a signaling molecule called ‘fibroblast growth factor 8’.
It was found to induce proliferation in progenitor and stem cell populations that also respond to amyloid-beta.
Now the researchers have identified this process, they can apply it to mice – and humans.
They hope to discover the equivalent cells in mammals – and induce them to proliferate by pulling the right triggers.
Dr Kizil added: “We will first address these questions using mouse as a model system.
“But eventually, we hope our research will uncover strategies to induce regeneration as a new therapeutic approach in Alzheimer’s disease in humans.”
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