16 August 2013

Alzheimer's disease: a paradigm shift?

Americans have proposed a new hypothesis of Alzheimer's disease

Copper newsResearchers from the Stanford University School of Medicine have proposed a fundamentally new hypothesis of the causes of Alzheimer's disease (AD).

They suggest that the disease is based on age-related disorders of the immune system of the brain, which leads to excessive accumulation of one of the key proteins of this system at synapses and their subsequent degeneration. The work was published on August 14 in the Journal of Neuroscience (Stephan et al., A Dramatic Increase of C1q Protein in the CNS during Normal Aging).

According to the most common "amyloid" theory, the underlying cause of AD – an incurable neurodegenerative disease – is the deposition of beta-amyloid protein in brain tissues, which leads to the accumulation of so–called amyloid plaques, degeneration of synapses - specific contacts between neurons that provide signal transmission from one nerve cell to another and, as a consequence, progressive cognitive dysfunction.

However, a group led by Ben Barres, examining the brain tissue of mice of different ages, came to the conclusion that it was all about a completely different protein. We are talking about the C1q protein, which is part of the so–called complement system consisting of 20 proteins - a cascade system involved in the implementation of the immune response, designed to protect the body from the action of foreign agents. C1q is a key element of this system, it is it that triggers the biochemical cascade of immune response reactions, first binding to potentially dangerous cells and thereby marking them as a target for attack by cells of the immune system.

Previously, it was believed that there was no complement system in the brain, but in 2007, Barres' group discovered that it was active in the rapidly developing brains of children. As it turned out, C1q is produced there by microglia cells – an analogue of immune system cells in the brain, and the remaining 19 complement system proteins are produced by neuroglial cells, astrocytes. This system is used in the growing brain to clear it of excess synapses that appear during development – complement proteins accumulate around such synapses, and microglial cells, focusing on them, destroy synapses.

In the course of the current study, Barres and his colleagues found that with age, the concentration of the C1q protein in the brain increases exponentially, reaching 300 times the initial level. For comparison, the level of age-related accumulations of other proteins is usually only 3-4 times higher than the initial indicators. And, most importantly, C1q concentrates around synapses, which makes them targets for attack by microglial cells, mainly in those regions of the brain that are particularly affected by neurodegenerative diseases – the hippocampus, the substantia nigra, the pear-shaped cortex.

Based on the results obtained, the authors suggest that AD is based on the following mechanism, some elements of which require further research: the hyperactivity of the complement system in the adult brain, which occurs for unknown reasons, characteristic of childhood, leads to overproduction of C1q by microglial cells, while the rest of the proteins of this system for some reason remain inactive. C1q accumulates in increasing concentration around synapses, for unknown reasons, not being removed from brain tissues naturally, and causes their degeneration on an ever-increasing scale.

According to Burris, quoted by FoxNews (A potential cure for Alzheimer's? Scientists discover new culprit behind brain-wasting disease), if we consider the genesis of AD within the framework of the proposed hypothesis, the formation of amyloid plaques is only one of the symptoms of the disease, and not its cause.

Burris believes that the discoveries made by his group can radically change the approach to AD therapy through the use of existing C1q inhibitors.

Portal "Eternal youth" http://vechnayamolodost.ru16.08.2013

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