ageing diseases – Lightsources.org

A new approach for finding Alzheimer’s treatments

2018/09/102018/09/20

Considering what little progress has been made finding drugs to treat Alzheimer’s disease, Maikel Rheinstädter decided to come at the problem from a totally different angle—perhaps the solution lay not with the peptide clusters known as senile plaques typically found in the brains of Alzheimer’s patients, but with the surrounding brain tissue that allowed those plaques to form in the first place.
It was a novel approach that paid off for Rheinstädter and his team of researchers from McMaster University who used the Canadian Light Source in Saskatoon as part of a study of the effect various compounds have on membranes in brain tissue and the possible impact on plaque formation.

“Alzheimer’s disease has interested me for a long time,” said Rheinstädter, a professor in the Department of Physics and Astronomy and the Origins Institute at McMaster. “It is something almost every Canadian will be affected by in their lives.”

Image: Adam Hitchcock, Adree Khondker and Maikel Rheinstädter.

Metallic drivers of Alzheimer’s disease

2018/05/172018/05/18

The detection of iron and calcium compounds in amyloid plaque cores

X-ray spectromicroscopy at the Scanning X-ray Microscopy beamline (I08), here at Diamond, has been utilised to pinpoint chemically reduced iron and calcium compounds within protein plaques derived from brains of Alzheimer’s disease patients. The study, published in Nanoscale, has shed light on the way in which metallic species contribute to the pathogenesis of Alzheimer’s disease and could help direct future therapies.

Alzheimer’s disease is a neurodegenerative disease that is associated with dementia and shortened life expectancy. The disease is characterised by the formation of protein plaques and tangles in the brain that impair function. As well as protein plaques, perturbed metal ion homeostasis is also linked with pathogenesis, and iron levels in particular are elevated in certain regions of the brain.

A team of scientists with a long history in exploring biomineralisation in Alzheimer’s brains set out to characterise the iron species that are associated with the amyloid protein plaques. They extracted samples from the brains of two deceased patients who had Alzheimer’s and applied synchrotron X-ray spectromicroscopy to differentiate the iron oxide phases in the samples.

They noted evidence that the chemical reduction of iron, and indeed the formation of a magnetic iron oxide called magnetite, which is not commonly found in the human brain, had occurred during amyloid plaque formation, a finding that could help inform the outcomes of future Alzheimer’s therapies.

Image: Synchrotron soft X-ray nano-imaging and spectromicroscopy reveals iron and calcium biomineralisation in Alzheimer’s disease amyloid plaques.

Analysing Alzheimer’s mechanisms with synchrotron light

2018/02/16

Researchers from the ALBA Synchrotron and the Universitat Autònoma de Barcelona (UAB) have analysed with synchrotron light different Alzheimer’s aggregates, their location and their effect in cultivated neuronal cells.

Results, published in Analytical Chemistry, pave the way to better understand the development of this disease that affects more than 30 million people worldwide.

Memory loss, communications’ difficulties, personality and behaviour changes, orientation problems … Unfortunately, these symptoms are widespread in our society, since 30 million people worldwide and 1.5 in Spain suffer from the effects of Alzheimer’s, according to the World Health Organization (WHO) and the Spanish Confederation of Family Members of Alzheimer’s and other dementias patients (CEAFA), respectively. Alzheimer’s is the most important cause of dementia and is described as a multifactorial disease that leads to neuronal cell death. Nowadays, there is no effective treatment to fight against or to prevent it.

When a person has Alzheimer’s, amyloid plaques are generated inside his brain. They are made of deposits or aggregates of the amyloid beta peptide. This peptide – which comes from a protein that is necessary for cellular functioning – tends to be aggregated by adopting different sizes and morphologies, depending on the physical and chemical conditions around it. Although it is already known that the presence of the beta amyloid peptide, together with other factors such as oxidative stress, play a key role in the onset and development of the Alzheimer’s disease, it is not still clear what causes the disease and what the consequences are.

>Read more on the ALBA website

Great experience at BioMAX

2017/06/302018/01/17

“It was a fantastic experience”, Jette Sandholm Kastrup.

On June 30, 2017 Professor Jette Sandholm Kastrup, University of Copenhagen was granted two shifts of beamtime at BioMAX by the Program Advisory Committee (PAC) and the MAX IV Laboratory Management for the project “Molecular recognition of agonists, antagonists and positive allosteric modulators at ionotropic glutamate receptors”.

The ionotropic glutamate receptors (iGluRs) are highly abundant in the central nervous system (CNS) and mediate fast synaptic neurotransmission. Dysfunction of the glutamatergic system has been associated with various diseases in the CNS, e.g. depression, Parkinson’s and Alzheimer’s diseases and epilepsy. The iGluRs are for example considered an attractive and appropriate target for the discovery of cognitive enhancers.

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