New breakthrough approach to atherosclerosis and Alzheimer's disease

Alzheimer's disease and atherosclerosis are diseases associated with chronic inflammation in the brain and blood vessels. Proteins of the immune system maintain these inflammations. A fat metabolism protein (ApoE), however, fights the inflammation and could be a role model in the future to stop it.

Approach to new therapies for atherosclerosis and Alzheimer's dementia

Researchers from the Ludwig-Maximilians-Universität München (LMU) in cooperation with the Leibniz Institute for Natural Product Research and Infection Biology in Jena and other partners have shown that the protein ApoE is a key molecule in the development of chronic inflammatory diseases and identified a promising one Approach to new therapies for atherosclerosis and Alzheimer's dementia. Their study results were published in the English journal "Nature Medicine".

A special protein opens up new options in the fight against arteriosclerosis and Alzheimer's disease. (Image: Design Cells / fotolia.com)

ApoE as key molecule and regulator

The researchers around Dr. Changjung Yin, Professor Andreas Habenicht and Professor Christian Weber of the Institute for Prophylaxis and Epidemiology of Circulatory Diseases (IPEK) at the LMU Clinic have shown that ApoE. Can cooperate with the Leibniz Institute for Natural Product Research and Infection Biology in Jena and other partners As a key molecule and regulator it intervenes in a central signaling cascade of the immune reaction, directly influencing inflammation. Thus, ApoE is not only associated with atherosclerosis, but also with Alzheimer's disease, AIDS and many other inflammatory diseases.

New starting point for the development of further therapies

By treating them with a drug that targets this cascade, scientists have been able to inhibit atherosclerosis and inflammatory processes in the brain. Thus, the IPEK researchers have identified a completely unexpected but above all common function of ApoE in different diseases and found a starting point for the development of new therapies for these diseases.

ApoE has a positive effect on cardiovascular diseases

In humans, there are three different variants of ApoE, which have a wide range of mechanisms of action, but their various functions have remained unclear. Since the early 1990s, it has been known that carriers of the ApoE4 variant have a higher risk of developing a specific form of Alzheimer's dementia. "Many Alzheimer's researchers consider ApoE to be harmful. However, in terms of cardiovascular disease, ApoE seems to have a positive effect: Mice that can not produce this protein because the gene has been knocked out show increased blood lipid levels and severe atherosclerosis, "says Yin.

How does ApoE deficiency affect the brain?

Alzheimer's disease is also known to be associated with inflammatory processes in the brain. To further characterize the function of the protein, the researchers investigated, among other things, how ApoE deficiency affects the brain. They found in an important structure in the brain of patients - the so-called choroid plexus - pathological fat deposits in the majority of diseased subjects and no or little deposits in healthy patients. The choroid plexus is a central braid in the brain responsible for, for example, the formation of the blood-brain barrier and brain metabolism, as well as the immigration of immune cells into the brain and therefore an important interface between the immune system, the cardiovascular system and the brain forms the brain. "These fat deposits are a whole new disease that was previously completely unknown," says Yin. "The more pronounced these deposits are, the sooner and more significantly the patients developed dementia."

Fat deposits trigger inflammatory processes

As researchers have shown, fat deposits trigger inflammatory processes by activating the so-called complement system, a signaling cascade of the immune system involving nearly 30 proteins. All human apo variants were able to attenuate this activation by binding to a particular protein of this system called C1q. Thus, ApoE was identified as the binding partner of C1q and as a direct and central regulator of this signaling cascade. C1q normally initiates activation of the classical complement system. "The resulting C1q-ApoE complex is found in places as diverse as the choroid plexus, Alzheimer's-type plaques in the brain, atherosclerotic arteries of the heart, arteries that supply the brain with blood, and the aorta. The number of complexes correlated with the degree of dementia of Alzheimer's patients and with the severity of atherosclerosis, "said Yin in a press release from LMU.

Further therapeutic approaches with ApoE

In addition to the classic, there are two additional activation pathways for the complement system, which do without C1q. When searching for new drugs to reduce the fatal inflammatory response, the scientists chose not C1q directly as a possible target, but a specific factor, which is a key component of all three activation pathways. "Indeed, we have been able to inhibit this factor by using a so-called small interfering RNA, siRNA for short," says Yin. "In this way, we were able to greatly reduce inflammatory reactions in the brain and atherosclerosis in mice. It could be that we were able to uncover a long-sought common mechanism of action of ApoE in different and previously difficult-to-treat inflammatory diseases, "the expert concluded. (Fm)