Alzheimer’s – Lightsources.org

Examining individual neurons from different perspectives

2021/09/022021/09/03

Correlative imaging of a single neuronal cell opens the door to profound multi-perspective sub-cellular examinations

Scientists combined two nano-imaging techniques that stand at opposite ends of the electromagnetic spectrum to demonstrate the benefits of correlative imaging to examine individual neurons from different perspectives.

To showcase this, they studied the molecular structures of amyloid proteins and investigated the role metal ions may play in the development of Alzheimer’s Disease at a previously never achieved resolution. Their detailed observations at the sub-cellular level underscore the potential of using combined nanospectroscopic tools to deal with uncertainties due to the complex nature of a biological sample.

Alzheimer’s Disease is the most common cause of dementia. Many research groups are working to reveal molecular mechanisms to better understand the process by which the disease evolves. Due to the current lack of effective treatments that could stop or prevent Alzheimer’s Disease, new approaches are necessary to find out how people can age without memory loss.

High-resolution microscopy techniques such as electron microscopy and immunofluorescence microscopy are most often used to detect amyloidogenic protein molecules, often considered key factors in the disease’s evolution. However, these commonly used methods generally lack the sensitivity necessary to depict molecular structures. This is why scientists from Lund University in collaboration with SOLEIL and MAX IV carried out a proof of concept study which showcases that combining two imaging modalities can be used as effective tools to assess structural and chemical information directly within a single cell.

Read more on the MAX IV website

Image: a O-PTIR setup: a pulsed, tunable IR laser is guided onto the sample surface (1). b X-ray fluorescence nanoimaging of individual neuronal cells deposited on Si3N4 (1). c Conceptualization of the data analysis based on superimposed optical, O-PTIR, and S-XRF images.

How a very “sociable” protein can hold clues about Alzheimer’s origin

2020/12/162020/12/17

The origin of the most prevalent form of Alzheimer’s disease, which accounts for 95% of cases, is still not clear despite decades of scientific studies. “Before understanding the pathology, we need to understand the biology”, explains Montse Soler López, scientist leading research on Alzheimer’s disease at the ESRF. “The only thing we are sure about is that the most common form of Alzheimer’s is linked with ageing”, she asserts.

So researchers have been focusing on parts of the body that degrade dramatically with age. Neurons, for example, are long-lived cells, meaning that they don’t renew themselves like other cells do. Neurons lodge mitochondria, which are so-called the “powerhouse of cell” because of their active role generating energy in the body. With time, mitochondria suffer oxidative stress and this leads to their malfunction. It has been recently discovered that people with Alzheimer’s may have an accumulation of amyloids inside mitochondria (previously it was thought amyloids were only outside the neurons). Montse Soler López is trying to find whether there is a link between mitochondrial dysfunction, presence of amyloids and early disease symptoms. “We believe that malfunctioning of the mitochondria can take place 20 years before the person shows symptoms of the disease”.

Read more on the ESRF website

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.

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

Combined imaging approach characterises plaques associated with Alzheimer’s disease

2017/12/052018/01/17

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.

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