Title: Defining metal biochemistry in Alzheimer’s: A key step towards effective diagnosis and treatment?
Funder: Alzheimer's Research UK

Abstract: Metals are vital for brain health, however when managed inappropriately they can cause brain damage, with metal imbalances being linked to the development of Alzheimer’s disease. These imbalances are associated with the formation of amyloid and tau lesions. Yet, our knowledge of metal biochemistry in Alzheimer’s lacks the chemical and spatial detail required to define how metals contribute to disease development, preventing effective metal targeting therapeutics for disease diagnosis/treatment. Using state-of-the-art x-ray techniques, our group is providing remarkable insights into Alzheimer’s biochemistry, including our discovery of elemental metallic nanoparticles within amyloid plaques. Metallic nanoparticles are chemically-reactive, generating free radicals which damage and kill brain cells. Metallic iron is strongly magnetic and can be observed using MRI. Thus metallic nanoparticles may represent biomarkers for disease diagnosis, and targets for therapies to treat Alzheimer’s by restoring healthy brain metal balance. Following these discoveries, I have advanced our investigations of Alzheimer’s metal chemistry, with provision for two more high-impact publications. We have active funding applications, and findings I will use to apply for research fellowships/projects. I request bridging funding to complete these activities and realize existing funding application outcomes. Support will be used to continue experimental work, including secured time at world-leading facilities.

Lay abstract: Metals are vital for brain health, however when managed inappropriately they can cause brain damage, with metal imbalances being linked to the development of Alzheimer’s disease. These imbalances are associated with the formation of amyloid and tau lesions. Yet, our knowledge of metal biochemistry in Alzheimer’s lacks the chemical and spatial detail required to define how metals contribute to disease development, preventing effective metal targeting therapeutics for disease diagnosis/treatment. Using state-of-the-art x-ray techniques, our group is providing remarkable insights into Alzheimer’s biochemistry, including our discovery of elemental metallic nanoparticles within amyloid plaques. Metallic nanoparticles are chemically-reactive, generating free radicals which damage and kill brain cells. Metallic iron is strongly magnetic and can be observed using MRI. Thus metallic nanoparticles may represent biomarkers for disease diagnosis, and targets for therapies to treat Alzheimer’s by restoring healthy brain metal balance. Following these discoveries, I have advanced our investigations of Alzheimer’s metal chemistry, with provision for two more high-impact publications. We have active funding applications, and findings I will use to apply for research fellowships/projects. I request bridging funding to complete these activities and realize existing funding application outcomes. Support will be used to continue experimental work, including secured time at world-leading facilities.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL