A new approach for finding Alzheimer’s treatments

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.”

>Read more on the Canadian Light Source website

Image: Adam Hitchcock, Adree Khondker and Maikel Rheinstädter.

Analysing Alzheimer’s mechanisms with synchrotron light

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

Combined imaging approach characterises plaques associated with Alzheimer’s disease

Australian Synchrotron X-ray and infrared imaging techniques have been used in a powerful combined approach to characterise the composition of amyloid plaques that are associated with Alzheimer’s disease.

Alzheimer’s disease is major international health problem that accounts for 50-75 per cent of all cases of dementia in Australia. More than 400,000 Australians are living with dementia and it is the second leading cause of death.

Amyloid plaques are complex protein fragments which accumulate between nerve cells in the brain and may destroy connections between them, and are hallmarks of Alzheimer’s disease.

“However, it is still not known if the plaques cause Alzheimer’s or whether the Alzheimer’s causes their formation, which is why we need to improve our understanding of protein structures within plaques, and the molecular and elemental composition of tissue surrounding the plaques“ said Dr Mark Hackett of Curtin University, who led the research.

The study was published earlier in the year in Biochemistry.

As very few methods provide sufficient chemical information to study the composition and distribution of the plaques in excised tissue, the investigators decided to combine Synchrotron spectroscopic techniques with additional imaging methods, Raman spectroscopy and fluorescence microscopy.

>Read more on the Australian synchrotron website

Image Caption: Histology, FTIR, XFM, and tissue autofluorescence imaging of Aβ-plaques