The distribution of brain biometals using a natural animal model for Alzheimer’s disease (AD) has been examined for the first time in a study led by researchers from the Centre for Healthy Brain Ageing (CHeBA), UNSW Sydney. The findings provide new insights into the progression of Alzheimer’s disease and may inform future drug developments to target the disease. The study was published in the journal, Frontiers in Aging Neuroscience.
Researchers found a significant and age-dependent rise in levels of iron, calcium, zinc, copper and aluminium in the brains of Octodon degus, a rodent which shows naturally occurring neuronal, neuropathological and behavioural abnormalities associated with sporadic or late-onset AD. The innovative study methodology, combining a natural animal model with laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS), overcomes current limitations in the research according to lead author and head of CHeBA’s Molecular Biology group Dr Nady Braidy.
“Currently, biometal accumulation can only be examined post-mortem in humans,” said lead author and head of CHeBA’s Molecular Biology group Dr Nady Braidy. “Studies using transgenic mice models are problematic because the disease progression may differ and many discoveries have been lost in human translation. The Octodon degus model allows us to examine various brain regions over time to understand the progression from early to late-stage sporadic Alzheimer’s, the most common form of the disease.”
The researchers identified higher levels of iron, calcium, zinc and copper in the cortex and hippocampus, the regions where amyloid plaques and other brain changes associated with AD are most commonly reported. Aluminium was found to be higher in the hippocampus alone. Age-related deregulation of metal trafficking pathways was observed, as well as impaired lysosomal function which is associated with digestion and waste removal.
Previous research has identified large concentrations of the biometals copper, iron and zinc in amyloid beta plaques, a typical feature found in the brains of patients with AD. These biometals are associated with oxidation, which damages cell membranes, proteins and DNA, and are believed to contribute to the pathobiology of AD. Better understanding of the trafficking pathways and micro-distribution of these biometals may help improved drug targeting.
“Given the role of abnormal biometal accumulation, treatment that bonds and removes heavy metals from the body, called metal chelation, may represent an important therapeutic strategy to prevent the onset or slow down the progression of AD,” said Dr Braidy.
Co-author and leader of CHeBA’s Proteomics group, Dr Anne Poljak, said the findings provide a rationale for further use of the “metallomic” approach in research and drug development to improve brain health outcomes.
Media contact: Heidi Douglass, Centre for Healthy Brain Ageing,
+61 2 9382 3398, 0435 579 202 | h.douglass@unsw.edu.au
+61 2 9382 3398, 0435 579 202 | h.douglass@unsw.edu.au
