Iron dyshomeostasis has been observed in Alzheimer’s Disease (AD) . We have suggested that ferroptosis, a form of iron-enhanced programmed cell death, operates in AD , and arises from excess lethal lipids as detoxification mechanisms are overwhelmed . We hypothesize that iron acts as an “accelerant” by enhancing lethal lipid production. Thus, attenuating iron levels while simultaneously increasing cellular detoxification may pose a novel putative therapeutic strategy for AD.
To develop state-of-the-art quantitative simultaneous mapping of brain iron and lethal lipids in the Alzheimer’s Disease brain towards identifying novel therapeutic targets.
Techniques and skills
Quantitative brain metal mapping by synchrotron radiation X-ray fluorescence
Quantitative mapping of brain lipids (lipidomics) by mass spectrometry or Raman imaging
Immunohistochemistry and microscopy
Annual Overarching Objectives
Development of tissue preparation methods for acquisition of iron and lipid maps, including training in techniques.
Development of analysis methods for information-rich lipid maps (lipidomics data), including training in image analysis.
Training in quantitative analysis of iron mapping data.
Co-registration of multimodality data
Development of artificial intelligence methods to enhance lipidomic and metal characterisation.
Data collection from human brain samples from AD and age-matched cognitively normal subjects
Quantification of iron mapping data
Analysis and quantification of experimental data including identification and quantification of toxic lipids and their precursors.
Writing research papers and thesis
 A Ashraf, M Clark, P-W So (2018). The aging of iron man. Fronts Aging Neursci. 10: 65.
 A Ashraf, J Jeandriens, HG Parkes, P-W So (2020). Iron dyshomeostasis, lipid peroxidation and perturbed expression of cystine/glutamate antiporter in Alzheimer’s disease: evidence of ferroptosis. Redox Biol 32: 101494.