Development Of Hyper-Polarized 129Xe Gas Magnetic Resonance Imaging-Based Molecular Probe for Early Detection of Alzheimer’s Disease
Alzheimer's disease (AD) is believed to be caused by a protein structure called amyloid oligomers, which are amyloid beta (Aβ) peptides that have been converted from individual molecules into a chain that has different molecular structure and properties. These amyloid oligomers occur on the surface of brain cells in advance of Alzheimer's symptoms. I propose to create a molecule which will bind to these oligomers and can be imaged using magnetic resonance imaging (MRI). This method would provide up to 10 years advance notice of AD. Early detection would permit preventative therapies to be started earlier, when they are more likely to be effective.
Our goal is to develop MRI techniques that can be used to detect AD up to 10 years before the start of Alzheimer`s symptoms. Currently, brain imaging of Alzheimer`s patients only confirms a diagnosis, whereas our approach seeks to predict a future diagnosis allowing for earlier treatment. Our approach is truly interdisciplinary as it combines biophysical research, synthetic chemistry and nuclear physics.
To accomplish this goal we plan to find molecules called affinity tags that attach to amyloid oligomers, which are proteins believed to cause AD. After being administered to patients, the affinity tags will attach to amyloid oligomers in their brain. Once we have identified affinity tags for amyloid oligomers, we will attach them to a molecule which can be detected by MRI. We will then test this molecule using MRI to ensure that it both attaches to amyloid oligomers and provides a detectable magnetic resonance signal. Next we can test these molecules in people with a family history of Alzheimer's disease and track them to see the predictive effectiveness of our MRI techniques.
About the Researcher
Francis Hane, PhD, completed his PhD in biophysics at the University of Waterloo under the supervision of Zoya Leonenko, PhD. Dr. Hane's PhD research focused on the aggregation of the amyloid-beta protein (implicated in AD) at the level of a single molecule using atomic force spectroscopy. Atomic force spectroscopy is a nanoscale technique used to probe the interactions between two molecules. An apt analogy is a fish hook stuck on the bottom of a lake with the fisherman pulling up on the rod. Eventually, the hook dislodges and is freed. Atomic force spectroscopy measures the force of pulling apart the molecules, and is similar to the fishing rod, but on a nanoscale. Since completing his PhD, Dr. Hane has worked in the lab of Mitchell S. Albert, PhD, the inventor of hyperpolarized (HP) gas MRI. Dr. Hane has been applying HP gas MRI to a variety of diseases including pulmonary inflammation and Alzheimer's disease.
"Ever since I was a young boy I was interested in science. I was the kid with a poster in my school locker explaining Einstein's famous mass-energy equivalence equation, E=mc2!
I remember my first experience with Alzheimer's disease. Our neighbour, Hans, an elderly gentleman and avid horticulturalist, suffered from it. The disease slowly robbed him of his ability to care for his garden and his wife [and] as his disease progressed, he could no longer care for himself. Little did I know that one day I would be studying ways to help millions of people who suffer in the way that Hans and his family did. The generous support of the BrightFocus Foundation and its donors are key ingredients in making progress."
Hane F, Augusta C, Bai O. A hierarchical Bayesian model to predict APOE4 genotype and the age of Alzheimer's disease onset. PLoS One. 2018 Jul 12;13(7):e0200263. doi: 10.1371/journal.pone.0200263. eCollection 2018. PubMed PMID: 30001420; PubMed Central PMCID: PMC6042730.
Robinson M, Lee BY, Hane FT. Recent Progress in Alzheimer's Disease Research, Part 2: Genetics and Epidemiology. J Alzheimers Dis. 2017;57(2):317-330. doi:10.3233/JAD-161149. PubMed PMID: 28211812; PubMed Central PMCID: PMC5366246.
Hane FT, Robinson M, Lee BY, Bai O, Leonenko Z, Albert MS. Recent Progress in Alzheimer's Disease Research, Part 3: Diagnosis and Treatment. J Alzheimers Dis. 2017 Mar 2. doi: 10.3233/JAD-160907. [Epub ahead of print] PubMed PMID: 28269772.
Hane FT, Li T, Smylie P, Pellizzari RM, Plata JA, DeBoef B, Albert MS. In vivo detection of cucurbituril, a hyperpolarized xenon contrast agent for a xenon magnetic resonance imaging biosensor. Sci Rep. 2017 Jan 20;7:41027. doi: 10.1038/srep41027.
Hane FT, Smylie PS, Li T, Ruberto J, Dowhos K, Ball I, Tomanek B, DeBoef B, Albert MS. HyperCEST detection of cucurbituril in whole blood using an ultrashort saturation Pre-pulse train. Contrast Media Mol Imaging. 2016 Apr 13. doi: 10.1002/cmmi.1690. [Epub ahead of print]
First published on: July 10, 2015
Last modified on: July 23, 2018