Alzheimer's disease in mice alleviated
Promising therapeutic approach for humans
Alzheimer's disease is one of the most common causes of dementia.The accumulation of particular abnormal proteins, including amyloid-ß (Aβ) among others, in patients' brains plays a central role in this disease. Prof. Frank Heppner from the Department of Neuropathology at Charité and his colleague Prof. Burkhard Becher from the Institute for Experimental Immunology at the University of Zurich were able to show that turning off particular cytokines reduced the Alzheimer's typical amyloid-ß deposits in mice with the disease. As a result, the strongest effects were demonstrated after reducing amyloid-ß by approximately 65 percent, when the immune molecule p40 was affected, which is a component of the cytokines interleukin (IL)-12 and -23.
Deficiency (or inhibition) of molecules of the interleukin (IL)-12 and/or IL-23 signal pathway reduces Alzheimer-like pathological changes – depicted here as so-called β-amyloid plaques (spot-like areas, stained in black) – substantially. Left: Brain hemisphere of an Alzheimer’s mouse; right: Brain hemisphere of an Alzheimer’s mouse without IL-12 receptor.
UZH
Relevant for human therapy
Follow-up experiments also relevant for humans showed that substantial improvements in behavioral testing resulted when mice were given the antibody blocking the immune molecule p40. This effect was also achieved when the mice were already showing symptoms of the disease. Based on the current study by Prof. Heppner's and Prof. Becher's team, the level of p40 molecules is higher in Alzheimer's patients' brain fluid, which is in agreement with a recently published study by American colleagues demonstrating increased p40 levels in blood plasma of subjects with Alzheimer's disease, thus showing obvious relevance for human therapy.
The significance of the immune system in Alzheimer's research is the focus of current efforts. Prof. Heppner and Prof. Becher suspect that cytokines IL-12 and IL-23 themselves are not causative in the pathology, and that the mechanism of the immune molecule p40 in Alzheimer's requires additional clarification. However, they are convinced that the results of their six-years of research work justify the step toward clinical studies in humans, for which they plan to collaborate with a suitable industrial partner.
In the context of other illnesses, such as psoriasis, a medication that suppresses p40 in humans has already been applied. "Based on the safety data in patients," comment Profs. Heppner and Becher, "clinical studies could now be implemented without delay. Now, the goal is to bring the new therapeutic approach to Alzheimer patients quickly."
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