22 July 2016

Amyloid plaques in the transparent brain

Transparent brain and 3D atlas of amyloid plaques

Maria Perepechaeva, "First-hand Science" based on Neuroscience News: Unexpected Arrangement of Plaques in Alzheimer's Affected Brains

Researchers from Rockefeller University (USA) used a newly developed imaging method that makes brain tissue transparent. This allowed them to see a three-dimensional picture of the location of clusters of pathological protein, beta-amyloid plaques, in the brains of deceased people suffering from Alzheimer's disease.

The presence and distribution of accumulations of the pathological beta-amyloid protein in the brain, which is considered a "trigger mechanism" for a chain of events leading to the death of neurons, was determined until recently by analyzing brain slices. Preparation of slices takes a lot of time, the subsequent three-dimensional reconstruction requires painstaking work and may be inaccurate. In any case, the resulting representation will be limited, because the brain is a complex three–dimensional structure with many interconnected components, which is difficult to fully reconstruct from the data of slices. I needed a way to see the big picture.

Such methods of spatial brain imaging as positron emission and functional magnetic resonance imaging show the activity of various brain areas, but they are unsuitable for studying the distribution of beta-amyloid. But the newly developed method called iDISCO (immunolabeling-enabled 3D imaging of solvent cleared organs) was just right.

Brain tissue is about 60% fat. If they are removed, the brain becomes, according to scientists, solid and transparent, almost "like glass." According to the iDISCO method, the brain is impregnated with a compound that gives fats an electric charge, and then exposed to an electric field with an opposite charge. It turns out a "magnet" that "pulls" fat from the brain.

The plaques themselves were stained using immunological methods, after which they became visible in volume - in the whole hemisphere of the mouse brain and in small fragments of the human brain. It turned out that in mice models of Alzheimer's disease, plaques are quite small, uniform in size and shape and are not grouped, unlike the brain of a sick person, where heterogeneity is visible, plaques are larger, and complex three-dimensional amyloid structures are observed.

amiloid.jpg
Clusters of beta-amyloid are colored purple

Scientists hope that by comparing the patient's symptoms and the postmortem picture of the distribution of beta-amyloid in his brain, it will be possible to learn to distinguish between types of Alzheimer's disease, which may turn out to be not one, but several conditions, because the number of amyloid plaques does not always correspond to the severity of the disease. Sometimes there are a lot of plaques, but dementia does not occur, and sometimes there do not seem to be plaques, but there are symptoms of the disease. Perhaps for this reason, clinical trials of the drugs being developed fail: because they have different efficacy in different variants of the disease. There is no way to distinguish these variants yet, and three-dimensional visualization of plaques, their location, and analysis of the structures they form can help to learn this.

Portal "Eternal youth" http://vechnayamolodost.ru  22.07.2016

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