Is beta-amyloid a component of innate immunity?
In the article "The Alzheimer's Disease-Associated Amyloid beta-Protein Is an Antimicrobial Peptide", published in the journal PLoS One on March 3, researchers working under the direction of Robert D. Moir from Massachusetts General Hospital describe the evidence they have obtained for the antimicrobial properties of beta-amyloid. Apparently, this protein is a component of innate immunity that protects the body from a wide range of pathogens.
Innate immunity is the body's first line of defense against pathogens penetrating it. The launch of the mechanisms of the innate immune response ensures the rapid mobilization of leukocytes and chemical factors, such as cytokines and antimicrobial peptides, to fight bacteria, viruses, fungi and even tumor cells. Antibodies and other components of the acquired immune response practically do not penetrate the brain tissues surrounded by the blood-brain barrier, therefore, the protection of the central nervous system from infections is mainly the task of antimicrobial peptides.
Beta-amyloid is toxic to neurons and its accumulation, leading to the appearance of characteristic plaques in the brain tissues of patients with Alzheimer's disease, is considered to be the cause of neurodegeneration symptoms developing with this disease. This protein is a product of enzymatic cleavage of larger precursor protein molecules, which forms several types of beta-amyloid molecules. The most common of them – beta-amyloid-40 and beta-amyloid-42 – are particularly prone to the formation of toxic plaques. It is known that beta-amyloid stimulates inflammatory processes, and its biological activity has so far been considered exclusively pathogenic. However, the authors have received evidence that beta-amyloid actually has antimicrobial properties and can play an important role in protecting the brain from infections.
At first, scientists noticed that beta-amyloid has a certain physical, chemical and biological similarity with antimicrobial proteins, especially human cathelicidin LL-37. In order to study this phenomenon, they conducted parallel testing of the microbicidal activity of beta-amyloids-40 and -42 and LL-37 using a panel of 15 of the most important pathogens. As a result, it turned out that beta-amyloid suppresses the growth of eight of them. At the same time, compared with LL-37, beta-amyloid-40 was more effective against seven, and beta-amyloid-42 was more effective against six of these microorganisms, including the yeast–like fungus Candida albicans and certain strains of listeria, streptococci and staphylococci.
To study the antimicrobial activity of beta-amyloid associated with Alzheimer's disease, the researchers tested the ability of postmortem samples of homogenized brain tissue of patients with Alzheimer's disease and control individuals of the same age to suppress the growth of the yeast-like fungus Candida albicans in culture. The highest concentration of beta-amyloid plaques is usually observed in the frontal lobes of the brain, and samples of these brain regions of patients with Alzheimer's disease significantly suppressed the growth of fungi, which was not observed in cultures in which control tissue samples were introduced. At the same time, the degree of microbicidal activity of the samples was directly proportional to the amount of beta-amyloid contained in them, and the introduction of antibodies to beta-amyloid into the culture resumed the growth of pathogens. The results of the second experiment, during which samples of cerebellar tissue were used, which is characterized by the lowest content of beta-amyloid, both in experimental and control formulations demonstrated the absence of antimicrobial activity.
The authors suggest that prolonged activation of the mechanisms of innate immunity as a result of chronic or transferred infection of the central nervous system may lead to excessive production and accumulation of beta-amyloid. Known risk factors for Alzheimer's disease, such as stroke, traumatic brain injury and exposure to certain anesthetics, can also trigger the mechanisms of an innate immune response and stimulate the production of beta-amyloid.
While a rare mutation that directly causes the development of a hereditary form of Alzheimer's disease stimulates the synthesis of beta-amyloid-42, several recently identified genes, presumably playing a role in the pathogenesis of the disease, are involved in the formation of innate immunity. Currently, researchers are testing the hypothesis that a complex of genetic factors can increase the likelihood of developing Alzheimer's disease by activating the mechanisms of innate immunity and, accordingly, stimulating the synthesis of beta-amyloid.
The authors believe that the identification of pathogens most prone to triggering the synthesis of beta-amyloid will allow the development of methods for the prevention and suppression of this mechanism, for example, through immunization.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru according to the materials of Massachusetts General Hospital: Alzheimer's-associated protein may be part of the innate immune system.
09.03.2010