With the rapidly progressing development of therapies for Alzheimer’s Disease (AD) treatment, comes the need for sensitive diagnostics. Within the Oxford-McGill-ZNZ Partnership, the groups of Dr. med. Luka Kulic, of the University of Zurich and Prof. Gerhard Multhaup of McGill University, have received a Velux Foundation grant to develop a diagnostic test for Alzheimer’s Disease based on a new amyloid-derived biomarker. ZNZ News talked with Luka Kulic about their plans.
ZNZ News: What is the main goal of the project?
Luka Kulic: Alzheimer’s disease (AD) is the leading cause of age-related 
cognitive and functional decline worldwide. It is more and more recognized that early intervention will offer the best therapeutic success and as the development of therapeutic approaches is rapidly progressing there is a need for sensitive diagnostics. In this project we want to establish a diagnostic assay for the early detection of individuals at risk for developing AD, based on a novel biomarker. The ultimate goal is to be able to use non-invasive sample material, such as peripheral blood for screening. This is, so to speak, the Holy Grail in AD diagnostics.
Which biomarker do you use and why is there a need for an alternative biomarker?
AD seems to be caused by an imbalance between Aβ production and clearance. In the early stages of the disease, Aβ is still effectively cleared from the brain. Our target molecule, Aβ34, is a product of this Aβ protease clearance pathway. We postulate that this molecule is an effective biomarker for early disease detection. Moreover, Aβ34 is more soluble and has a lower tendency to aggregate than other currently used biomarkers for AD, making it a promising candidate for sensitive detection in e.g. blood.
What indications do you have that Aβ34 can have a predictive value?
As part of a preliminary McGill-Zurich pilot study, supported by the partnership initiative brain@McGill, we have used our optimized Aβ34 ELISA to analyze a series of human samples for clinically relevant Aβ levels. We have compared patients with Mild Cognitive Impairment (MCI), these patients are known to have a high risk of developing AD, and healthy subjects and found that Aβ34 was significantly elevated in CSF samples from MCI patients, when compared to healthy individuals, while the corresponding levels of other forms appeared to be unaltered. We even have some data from retrospective studies that support the predictive value of the test: MCI patients with elevated CSF Aβ34 levels did go on to develop AD, whereas MCI patients with lower Aβ34 levels did not.
How does the collaboration with McGill work?
Our study has just started, but the collaboration with McGill goes back 1,5 years. It all started with a three months visit of a PhD student from McGill in our lab. As the results were very promising, we have extended the collaboration. PhD and postdoctoral students are working on this joint project in Zurich and in Montreal. We, in Zurich, contribute the clinical part; we provide patient material and do clinical studies, as well as additional lab work such as histology on patient brain material and in a mouse models.
The focus and expertise of Prof. Multhaup’s group at McGill is on biochemical pharmacology. His group will work on improving the assay platform to make the detection threshold for the amyloid degradation product as low as possible.
More information:
- Zurich based Velux Stiftung is a charitable Foundation supporting Research about Daylight, Healthy Aging and Ophthalmology, see veluxstiftung.ch
- Gerhard Multhaup, Dr. rer. nat. Professor and Chair Department of Pharmacology & Therapeutics McGill University, Montreal, Quebec, Canada, website
- Luka Kulic, Dr. med. Group Leader and Attending Physician Institute for Regenerative Medicine (IREM), University of Zurich, Schlieren, Switzerland, website