Alzheimer's is the most common form of dementia. The symptoms first show up when the disease has already reached an unstoppable stage. Although no effective medication has been found, science has reason to be hopeful.
Bonn is one of the centers of German research into Alzheimer's disease. Two major research organisations work here: the German Center for Neurodegenerative Diseases (DZNE) and the Center of Advanced European Studies and Research (caesar). Scientists from both teams are currently working together to find a medical solution to Alzheimer's.
Alzheimer's differs considerably from other diseases of the nervous system: it destroys the patient's memory, especially the episodic memory which records autobiographical events. Gabor Petzold, a researcher at the DZNE, relates the type of things that get forgotten: "Where did I park my car? When did I last go shopping? When did I get married? In which city do I live?"
Able to drive - but where is the car?
Alzheimer's patients often appear physically healthy. Their procedural memory, which is responsible for movements and body control, is only affected once the illness is far advanced. "There are things that the body has learned, which don't have to be actively recalled, like driving a car or riding a bike," according to Petzold.
Two regular proteins in the nerve cells are responsible for the disease: the amyloid-beta protein and the tau protein. Alzheimer's first appears when the concentration of these proteins increases and they start to clump together, eventually resulting in deposits or so-called brain plaque.
The amyloid-beta protein clumps together outside of the nerve cells, the tau protein inside of the cells. That, in turn, destroys the nerve cord and the synapses, which are responsible for transporting information between cells.
Therapies hampered by negative side effects
There currently is no effective medical cure for Alzheimer's, but researchers are pursuing several potentially promising avenues. The various options all have one thing in common: they aim to reduce the concentration and clumping of both proteins - either by transporting the proteins out of the brain or by reducing the clumping in the first place.
One option could be a vaccine, says neuro immunologist Annett Halle from caesar research institute. "There is an active vaccination. You encourage the immune system to form an antigen that counteracts the amyloid-beta protein. This can help reduce the concentration of the protein in the brain and the clumping."
The idea is good, but there are problems. Experiments conducted on mice showed a reduction in the brain plaque. But achieving this in humans won't be so simple, as there were serious side effects. "The immune system over-reacted and there were infections," said the neurologist. "A larger study had to be broken off."
Alzheimer's is caused by a build up of two proteins: the amyloid-beta and the tau
Activating immune cells called mikroglia cells, which are able to attack amyloid-beta proteins and transport them out of the brain, has not yet worked. In laboratory tests Annett Halle discovered that too many immune cells end up damaging the very nerve cells they are meant to protect.
Another option currently pursued by the researchers is the blocking of particular enzymes, so-called secretases, which form the ameloid-beta protein from another protein. But here there is also a snag - some of these enzymes are not only responsible for the creation of amyloid-beta proteins, but also for other important processes in the brain.
Which protein is more important?
The neurologist Eva-Maria Mandelkow and her husband, Eckhard Mandelkow, believe that therapies should target the tau protein rather than the amyloid-beta. "We believe the tau protein is what makes the nerve cells die," Ms Mandelkow said.
In tests on specially bred mice that had a predisposition for Alzheimer's, the two researchers were able to prove that dementia began when the tau protein clumps were formed. After stopping the formation of tau proteins through genetic manipulation, the scientists were able to give back memory to mice that already had dementia.
In fact, the mice were able to learn actively again after just four weeks. However, because the recovery was achieved via a genetic trick usable only for mice, the results are not transferrable to humans. Still, for Eckard Mandelkow, the results are the key to success in combatting the disease.
Searching for the right substance
"If it is possible to stop the effect of the tau protein, then we have won, because it means the synapses can be re-established again," says the specialist for virus proteins. For this reason the Mandelkows are concentating their research on finding a substance that stops the clumping together of tau proteins.
The two researchers have looked at over 200,000 substances. "We have have found a few that don't just reduce the clumping together of the tau protein in the test tube, but that also dissolve the clumps," said Eva-Maria Mandelkow.
Although it doesn't yet work for humans, there has been success in experiments conducted on worms. Worms rendered immobile by accumulated tau protein deposits were able to move again after receiving a so-called aggregation inhibitor.
It's likely to be some time before such medication can be developed for humans. But even now, people can actively delay the onset of Alzheimer's, Mandelkow says, by staying fit through sport. In her research, she was able to show that mice that ran a lot tend to get dementia much later. High blood pressure and diabetes are also known to be potential catalysts for the disease.
Author: Fabian Schmidt / al
Editor: Neil King