The mechanisms of the Alzheimer´s development: visible in the light of the ALBA Synchrotron .

Researchers at the ALBA Synchrotron and from the Autonnomous University of Barcerlona (UAB) using synchotron light have analyzed how are, where are located and which effects have different Alzheimer´s aggregates within in vitro neurons. 

 

Inside the facilitie of the ALBA´s Synchrotron.

 

Their discoveries show by the first time the in situ co-localization of the amorphous amyloid peptide aggregates near to the sites with the most oxidative stress (with great quantity of oxidative macromolecules), which represent the main initial causes of the Alzheimer´s development. 

Results have been published in Analytical Chemistry magazine in colaboration with scientists from the ERSF european Synchrotron, and open the way to better understand how this disease is developed which affects more than 30 millions people in the world, regarding to dates from the  OMS.

In order to carry out these studies researchers have used the analytical capacity of the Alba (Barcelona,Spain) and ERSF (Grenoble, France) Sinchrotrons, which are electrons accelerators facilities  that produce differents light types, them allow to visualize the atomic and molecular structure from the materials and thus study their properties.

 

Representation of the molecular structura Source Pixabay.

 

In this study they have used infra-red light, which is absorved by the bonds between molecules allowing to know which is the chemical composition of a sample. In turn, this light beam is collected by a microscope, allowing to know the molecular distribution of it.

 

Is thanks to the great brightness of the synchrotron light, that this distribution can be measured at very high espatial resolutions.  

 

This technique has allowed to analyze the effect of two types of amyloid peptide aggregates (fibrillars and amorphous) with which have been treated cultured neural cells.The results show that the amorphous aggregates trigger a higher oxidation degree than the fibrillars.

Neuron cells. Source Pixabay.

These results are in coherence with previous investigations overtaken in affected brains samples, where it was seen that the oxidation was higher in the regions that were surrounding the amiloid plaques and agree with the hypothesis that the amiloid petides are the triggers of the celular oxidation which is associated with the Alzheimer´s disease.

Visible images and infrared map of the analyzed aggregates of amyloid peptide (fibrillar and amorphous) in cultured neuronal cells. Black lines are drawn in order to mark the position of the peptide aggregates. Color scale (10 µm) corresponds to intensity: blue, low intensity; red, high intensity. 

 

The research, directed by Josep Cladera from the UAB, has served in order to make a new step in the characterization of these amorphous aggregates and to consider them like a potencial toxic agents in the begining of the disease´s development.

 

“This work is consistent with the hypothesis that amyloid peptides, especially in non-fibrillar forms, are capable of oxidizing cells, a key point for the development of the disease. Thanks to the infrared light, not only we can analyse the effects of these aggregates, but also we can relate them with the structure of peptides when they generate different aggregates. This can be of great importance for identifying the toxic causes of the disease”, says Núria Benseny, researcher from the MIRAS beamline at the ALBA Synchrotron.

 

Núria Benseny, researcher from the MIRAS beamline at the ALBA Synchrotron.

This advance allows to better understand how function the mechanisms by which proteins and amiloids peptides become toxics in the Alzheimer´s disease, illness that sufer currently more than 1,5 millions  people in Spain, regarding to the dates from the CEAFA.

Reference: “Synchrotron-based µFTIR study on the effect of Alzheimer’s Aβ amorphous and fibrillar aggregates on PC12 cells” Nuria Benseny-Cases, Elena Álvarez-Marimon, Hiram A. Castillo-Michel, Marine Cotte, Carlos Falcon, and Josep Cladera. DOI: 10.1021/acs.analchem.7b04818 

 

Do you want to know more about ALBA´s Synchrotron?

 

Scheme of the ALBA´s synchrotron.

It is a third generation scientific facilitie located at Cerdanyola del Vallès (Barcelona).

It is 270 meter perimeter and has 17 straight sections all of which are available for the installation of insertion devices.

The 3 GeV electron beam energy at ALBA is achieved by combining a LInear ACcelerator (LINAC) and a low-emittance, full-energy BOOSTER placed in the same tunnel as the STORAGE RING.

Life Science Laboratory, source Pixabay.

ALBA currently has eight operational state-of-the-art beamlines, comprising soft and hard X-rays, which are devoted mainly to biosciencescondensed matter (magnetic and electronic properties, nanoscience) and materials science.

Additionally, two beamlines are in construction (low-energy ultra-high-resolution angular photoemission for complex materials and microfocus for macromolecular crystallography).

 

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