Research News
Mouse brain with Alzheimer plaques (in red) and microglia (brownish). The microglia try to clear the brain from beta-amyloid. However, the toxicity of beta amyloid also kills these cells or at least compromizes their function substantially. Image: DZNE/Universität Rostock
More information:
www.helmholtz.de/dzne-alzheimer-plaques
www.helmholtz.de/alzforum-english
REFERENCE: M Krohn*, C Lange*, J Hofrichter, K Scheffler, J Stenzel, J Steffen, T Schumacher, T Brüning, AS Plath, F Alfen, A Schmidt, F Winter, K Rateitschak, A Wree, J Gsponer, LC Walker, and J Pahnke: Cerebral amyloid-β proteostasis is highly regulated by the membrane transport protein ABCC1 in mice, published in: The Journal of Clinical Investigation, http://www.jci.org/articles/view/57867
Prof. Dr Dr Jens Pahnke is currently still active at the DZNE site at the University of Rostock, but will relocate to the DNZE site at the University of Magdeburg in December 2011.
Washing Away Alzheimer's? A Vision for the Future
In spite of remarkable progress in researching the Alzheimer's disease, to this day there is no effective treatment targeting the cause. A main characteristic of the disease are accretions, so-called plaques, composed of the protein amyloid beta, which are found posthumously in the brain of Alzheimer's patients. How about it then, if the formation of such accretions could be prevented during one's lifetime already? Prof. Dr Jens Pahnke from the German Centre for Neurodegenerative Diseases (DZNE) and his research team now have achieved this goal in mice. The results could signify a breakthrough.
For their purposes, Pahnke and his team worked with genetically altered mouse lines lacking various ABC transport molecules. ABC transporters are involved in transporting various compounds or metabolites across the blood-brain barrier. The researchers were able to show that the toxic Alzheimer's amyloid was accreted in the mice's brain in 12 to 14-times the normal amount, if the transport molecule ABCC1 was inactive. The experimental data were fed into a mathematical model calculating the onset and course of the disease. The research project included also colleagues from the Emory University, Atlanta and the University of British Columbia, Vancouver. In a next step, they searched for an active agent to activate ABCC1 in a therapeutic, targeted manner. Thiethylperazine, which is used in the USA for treating nausea and vomiting, proved to be suitable.
When treating the Alzheimer's mice with thiethylperazine, the amyloid amount in their brains decreased by approximately 70 per cent within 25 days. In younger mice with a genetic disposition for Alzheimer's, this treatment prevented the formation of plaques, whereas it had a therapeutic effect in older mice already displaying the symptoms of the disease. The research group around Pahnke now works also on non-invasive imaging processes to examine in vivo in how far the activity of certain transport molecules is connected to the formation of accretions. "We assume that the reduced transport activity in specific areas of the brain results in accumulation of proteins and thereby to neurodegenerative diseases, not only of the Alzheimer's type", explains Pahnke. As of 2012, the team will be searching for older people suffering from Alzheimer's or Parkinson's disease or with a corresponding family history for participation in a genetic study and first pre-tests.
