Methods for the diagnosis of Alzheimer’s disease (AD) today typically rely on a combination of medical history, cognitive and neurological functioning assessments, as well as brain imaging a handful of molecular tests. Now, analytical geochemists at the University of Melbourne, Australia, say they developed a blood test to detect levels of potassium isotopes in the blood, which could be an effective biomarker for the early detection of AD.
The investigators’ discovery leveraged unlikely methods: inorganic analytical geochemistry techniques that originally were developed for cosmochemistry to better understand the formation and evolution of the Earth, Moon, planets, and asteroids. These were adapted to develop a highly sensitive method to search human blood for early biomarkers of the disease.
For their small pilot study, the researchers analyzed blood samples from 20 people—10 healthy subjects and 10 patients with AD from the Australian Imaging, Biomarker and Lifestyle (AIBL) study and biobank. Using their adapted methods, the team then compared levels of potassium isotopes in blood serum of the subjects.
“Our minimally invasive test assesses the relative levels of potassium isotopes in human blood serum and shows potential to diagnose AD before cognitive decline or other disease symptoms become apparent, so action can be taken to reduce the impacts,” said Brandon Mahan, PhD, a trace element and isotope geochemist, the School of Geography, Earth & Atmospheric Sciences, University of Melbourne, and first author of the study which is published in the journal Metallomics.
Mahan also noted that their test is scalable and, because it is an inorganic test, it doesn’t suffer from stability issues that could result from protein-based tests breaking down over time.
The study by the Melbourne team was spurred by a growing body of research that has identified the presence of brain biometals in AD patients. This has attracted scientists from the isotope metallomics field which has adapted existing geochemistry techniques to characterize the abundance and distribution of biometal isotopes in biological systems.
“For biometals in relation to neurodegenerative diseases such as AD, it has been observed that metals including Ca (calcium), Fe (iron), Cu (copper), and Zn (zinc) accumulate in the brain as a function of age and/or the development of neurodegenerative disorders (e.g. AD), where most metals are linked to the presence and/or aggregation of amyloid beta fibrils and the development of senile plaques,” the researchers wrote.
Other research has found that brains affected by AD also show deficits in certain metals including potassium and that such deficits may occur as early as middle age, making it a potentially important biomarker for early detection.
“Earlier diagnosis would enable earlier lifestyle changes and medication that can help slow disease progression and would allow more time for affected families to take action to reduce the social, emotional and financial impacts of dementia,” Mahan said. “It could also make patients eligible for a wider variety of clinical trials, which advance research and may provide further medical benefits.”
Added co-author Ashley Bush, PhD, a professor of neuroscience at the Florey Department of Neuroscience and Mental Health, University of Melbourne: “Our blood test successfully identified AD and shows diagnostic power that could rival leading blood tests currently used in clinical diagnosis.”
The Melbourne research team is now seeking collaborators to continue their work in a larger cohort of patients to further refine the use of potassium isotopes as an early AD biomarker.
