Assessment of melanotransferrin as an Alzheimer’s disease biomarker
Millions people worldwide are currently afflicted with Alzheimer’s disease (AD). In the absence of a complete understanding of the disease, therapeutic trials have been unsuccessful and there still remains no cure. Biomarkers that can reliably detect AD at the earliest possible stage are essential for disease monitoring and drug therapy. The development of a biomarker for AD that can be translated to a rodent model of AD would also be useful in drug discovery. A validated biomarker could profoundly change the rate of the development and implementation of treatments for AD by enabling rapid high throughput screening of new drugs. Furthermore, the development of a robust method for biomarker detection which can be translated to a clinical laboratory setting would be an invaluable tool for AD diagnosis and monitoring. AD patients have deposits of proteinaceous plaques within their brains.
Our previous research has shown that a protein called melanotransferrin (MTf; also known as p97 or CD228) exists at high levels in humans with AD and is specifically expressed by immune cells associated with plaques in the brain. In contrast, healthy patients show a limited distribution of MTf. Of particular interest, the blood concentration of p97 is also elevated in AD patients compared to age-matched healthy human controls. These preliminary studies are promising but suffer from limited population size and the inherent uncertainty of current AD diagnostic methods (i.e. can only be truly diagnosed post mortem).
We plan to further validate MTf as an AD biomarker in mouse models of AD. This will be accomplished using a revolutionary diagnostic technology known as the SISCAPA assay. This platform offers reliable, robust absolute quantitation of proteins in complex biological fluids, and is already in use across the USA for the diagnosis of thyroid cancer. Using this clinically amenable method, we will monitor AD model mice, and wild type controls, throughout their life and correlate MTf concentration with the degree of neurodegeneration. It is expected that at a young age AD mice will be indistinguishable from healthy controls but as plaques appear in the brain, so too will MTf levels rise. These results will illuminate the timeline and intensity of MTf elevation as it relates to neuropathology. We will also establish the baseline for MTf in healthy or pre-AD subjects. These discoveries have the potential to change the course of detection and treatment of AD.
Brett Eyford was one of the exceptional scientists identified to be a research grant recipient for the 2015 Trainee Partnership Award, co-funded by The Pacific Alzheimer Research Foundation (PARF) and the Michael Smith Foundation for Health Research (MSFHR). > Learn more…