Search for a Cure

The fight against forgetting: zebra fish help understand Alzheimer's

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Cell death can be imaged at single cell resolution in living zebrafish larvae 

(Paquet et al. 2009, J Clin Invest 119; 1382 - 1395)

The object of the study: the
zebra fish. Photo: LMU Munich
It is more than a hundred years since Alois Alzheimer first described the disease that is named after him. Alzheimer's disease is an illness in which nerve cells in the brain slowly die off. People affected by Alzheimer's suffer from impaired memory and orientation, and their capacity for thinking and judgment is restricted. These impairments make it increasingly difficult to cope with normal everyday life. The patients are increasingly reliant on help and support. Alzheimer’s disease can occur in people below the age of 50, but it is usually older persons who are affected. In the brain of Alzheimer’s patients, characteristic protein deposits (amyloid plaques) can be detected under the microscope, but in spite of intensive research there are still no drugs that can stop this illness.

Prof. Dr. C. Haass of the German Centre for Neurodegenerative Diseases at the Ludwig Maximilian University in Munich has been investigating the molecular causes of Alzheimer’s disease for some years now. In order to test new approaches to treatment however, animal models are required that can be used to track the illness and the therapeutic capabilities of drug treatments. As a suitable animal model, Prof. Haass has chosen the zebra fish.

This is a small fish that is transparent as an embryo, so that one can follow the developments and changes that occur inside the fish. Five years ago he brought the developmental biologist Dr. Bettina Schmid into his team to construct a large fish facility. Thousands of zebra fish are bred in this facility. Doctoral researcher Dominik Paquet has modified some of the fishes in such a way that they carry human genes inside them, which in a human being would lead to dementia. The fishes are now developing the characteristic signs that are also found in the brains of Alzheimer’s patients: the typical deposits in the nerve cells, followed by the dying off of the cells.

Alois Alzheimer's lab in Munich
Photo: LMU Munich
In all previous animal models, the loss of nerve cells could only be shown after death, if at all. In contrast to this, using the modified zebra fish it is possible for the first time to track the cell death in the living organism ‘live’. The transparent zebra fish embryos can be observed over extended periods under a laser microscope. If one then inserts a dye into the water that selectively colours dying cells, one can actually look cell death straight in the eye.

This discovery enables the researchers to now search specifically for medicines that delay cell death in the brains of Alzheimer's patients. Research assistant Frauke van Bebber is testing one of these medicines in the "Alzheimer’s fish", and is about to find out whether administering the medicine causes fewer cells to die or not.

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