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Studying Alzheimer's disease more directly with laser microscopy

8 April 2022
A team of scientists from VU and Amsterdam UMC, led by Freek Ariese and Johannes de Boer, conducted research using advanced laser-microscopic methods into the composition of so-called 'plaques' in the brains of deceased Alzheimer's patients.

With this new method, the scientists obtained direct information about the biochemical composition of the plaques. This contributes to a better understanding of Alzheimer's disease.

The research was published in the Journal of Optics and was conducted at the VU LaserLaB, in collaboration with the Pathology department of Amsterdam UMC, location VUmc. The research results were obtained during a bachelor's research project by Loes Ettema, who was a third-year student of Medical Natural Sciences during the research.

Misfolded
Alzheimer’s Disease is the most common cause of dementia and is characterised by the presence in the brain of so-called amyloid-beta plaques, which are deposits of insoluble, misfolded protein fragments. The plaques produce inflammatory molecules which bring damage to neurons and therefore to the brain.

Currently, histopathology is the gold standard for 'post mortem' diagnosis. With this technique the brain tissue is being labelled. However, the technique is invasive, labour intensive and does not provide direct information on the biochemical composition of the plaque. In this new VU research, a combination of (laser) microscopy techniques has been used to study these plaques  in a direct manner, without the need of colour labelling.

In this research, plaques in brain sections were located with a fluorescence microscope. Illuminating the brain with light, the researchers found that at least two different fluorescent compounds are present at (about) the same location in the plaque. In addition, with the help of Raman spectroscopy they found that some components, namely lipids and proteins, have a conformation in the plaque different from their conformation at other locations in the brain section. This showed the presence of misfolded protein. These findings were confirmed using a much faster technique: Stimulated Raman Scattering (SRS).

Vegetables and fruit
Besides changes in the structure of the compounds, compounds which are normally not present in the brain were detected too: all investigated plaques were found to contain carotenoids. This has never been demonstrated before. Carotenoids are present in vegetables and fruit and it is known that the human body uses carotenoids as antioxidants to fight infections. These compounds thus seem to try to protect the brain against Alzheimer’s Disease. To reveal which carotenoids are possibly present in plaques, reference measurements were performed on six different carotenoid connections. Based on these measurements, the presence of lycopene seems most probable, but this needs to be further investigated.