Eyes Provide Peek at Alzheimer’s Disease Risk

Protein deposits in retina and brain appear to parallel possible neurodegeneration, an insight that might lead to easier, quicker detection. Amyloid plaques are protein deposits that collect between brain cells, hindering function and eventually leading to neuronal death. They are considered a hallmark of Alzheimer’s disease (AD), and the focus of multiple investigations designed to reduce or prevent their formation, including the nationwide A4 study.

But amyloid deposits may also occur in the retina of the eye, often in patients clinically diagnosed with AD, suggesting similar pathologies in both organs. In a small, cross-sectional study, a team of researchers, led by scientists at University of California San Diego School of Medicine, compared tests of retinal and brain amyloids in patients from the A4 study and another study (Longitudinal Evaluation of Amyloid Risk and Neurodegeneration) assessing neurodegeneration risk in persons with low levels of amyloid.

Like the proverbial “windows to the soul,” the researchers observed that the presence of retinal spots in the eyes correlated with brain scans showing higher levels of cerebral amyloid. The finding suggests that non-invasive retinal imaging may be useful as a biomarker for detecting early-stage AD risk.

Amyloid deposits tagged by curcumin fluoresce in a retinal scan.

This was a small initial dataset from the screening visit. It involved eight patients,” said senior author Robert Rissman, PhD, professor of neurosciences at UC San Diego School of Medicine. “But these findings are encouraging because they suggest it may be possible to determine the onset, spread and morphology of AD — a preclinical diagnosis — using retinal imaging, rather than more difficult and costly brain scans. We look forward to seeing the results of additional timepoint retinal scans and the impact of solanezumab (a monoclonal antibody) on retinal imaging. Unfortunately we will need to wait to see and analyze these data when the A4 trial is completed.”

The findings published in the journal Alzheimer’s & Dementia.


Brain Metals Drive Alzheimer’s Progression

Alzheimer’s disease could be better treated, thanks to a breakthrough discovery of the properties of the metals in the brain involved in the progression of the neurodegenerative condition, by an international research collaboration including the University of Warwick.

Iron is an essential element in the brain, so it is critical to understand how its management is affected in Alzheimer’s disease. The advanced X-ray techniques that we used in this study have delivered a step-change in the level of information that we can obtain about iron chemistry in the amyloid plaques. We are excited to have these new insights into how amyloid plaque formation influences iron chemistry in the human brain, as our findings coincide with efforts by others to treat Alzheimer’s disease with iron-modifying drugs,” commented Dr Joanna Collingwood, from Warwick’s School of Engineering, who was part of a research team which characterised iron species associated with the formation of amyloid protein plaques in the human brainabnormal clusters of proteins in the brain. The formation of these plaques is associated with toxicity which causes cell and tissue death, leading to mental deterioration in Alzheimer’s patients.

They found that in brains affected by Alzheimer’s, several chemically-reduced iron species including a proliferation of a magnetic iron oxide called magnetite – which is not commonly found in the human brainoccur in the amyloid protein plaques. The team had previously shown that these minerals can form when iron and the amyloid protein interact with each other. Thanks to advanced measurement capabilities at synchrotron X-ray facilities in the UK and USA, including the Diamond Light Source I08 beamline in Oxfordshire, the team has now shown detailed evidence that these processes took place in the brains of individuals who had Alzheimer’s disease. They also made unique observations about the forms of calcium minerals present in the amyloid plaques.

The team, led by an EPSRC-funded collaboration between University of Warwick and Keele University – and which includes researchers from University of Florida and The University of Texas at San Antonio – made their discovery by extracting amyloid plaque cores from two deceased patients who had a formal diagnosis of Alzheimer’s. The researchers scanned the plaque cores using state-of-the-art X-ray microscopy at the Advanced Light Source in Berkeley, USA and at beamline I08 at the Diamond Light Source synchrotron in Oxfordshire, to determine the chemical properties of the minerals within them.

Source: https://warwick.ac.uk/