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Axel Montagne, Ph.D.
Principal Investigator (axel.montagne@ed.ac.uk)


Short Bio

Dr. Axel Montagne joined the UK DRI at Edinburgh in December 2020. He completed his PhD degree at the University of Caen Normandy (France) in 2012, followed by a postdoctoral training at the University of Southern California (USC) in Los Angeles from 2013 to 2016. Axel rapidly became Assistant then Associate Professor at USC in 2016 and 2020, respectively. His carrier has been focusing on how cerebrovascular dysfunctions contribute to neurodegeneration and dementia in both animal models and humans. In this UK DRI project, he combines molecular approaches with rodent non-invasive imaging, particularly MRI and PET, to study the causes and effects of blood-brain barrier (BBB) dysfunction, with a particular focus on the pericyte-endothelial crosstalk, in the context of neurodegenerative disease.


B.S. (2007)
Biology & Neurosience, University of Caen Normandy (France)

M.S. (2009)
Neurosience & Neuroimaging, University of Caen Normandy (France)

Ph.D. (2012)
Molecular and Cellular Aspects of Biology – Neuroscience & Neuroimaging (w/ Denis Vivien, Ph.D.), University of Caen Normandy (France)

Postdoctoral Training (2013-2016)
Department Physiology and Biophysics, University of Southern California (United States), Zilkha Neurogenetic Institute (w/ Berislav Zlokovic, M.D., Ph.D.)

Assistant Professor of Research (2016-2020)
Department Physiology and Neuroscience, University of Southern California (United States), Zilkha Neurogenetic Institute (w/ Berislav Zlokovic, M.D., Ph.D.)

Assistant Director (2016-2020)
Functional Biological Imaging Core (PET-MR 7T Animal System), University of Southern California (United States), Zilkha Neurogenetic Institute (w/ Russell Jacobs, Ph.D.)

Associate Professor of Research (Apr 2020-Dec 2020)
Department Physiology and Neuroscience, University of Southern California (United States), Zilkha Neurogenetic Institute (w/ Berislav Zlokovic, M.D., Ph.D.)

Associate Director (Jul 2020-Dec 2020)
Functional Biological Imaging Core (PET-MR 7T Animal System), University of Southern California (United States), Zilkha Neurogenetic Institute (w/ Russell Jacobs, Ph.D.)

Chancellor’s Fellow / Group Leader (Dec 2020-)
UK Dementia Research Institute at the University of Edinburgh, Centre for Clinical Brain Sciences (CCBS), Chancellor’s Building (Scotland)


My Career Contributions

I believe that some of my most important contributions have already impacted our research field, not only by improving our knowledge and understanding on the vascular link to neurodegeneration and dementia, but also by providing novel imaging technologies. I will briefly highlight below my key pre-clinical findings followed by important clinical studies.

A decade ago, I developed molecular magnetic resonance imaging (MRI) of neuroinflammation using iron oxide particles which target inflamed vessels (Montagne et al., Neuroimage 2012). This approach exhibits clinical potential to identify patients that would be most likely to benefit from anti-inflammatory treatment in several neuropathological conditions including stroke, AD and related dementias. More recently, I developed and used novel cutting-edge imaging methods to show that capillary breakdown initiates white matter (WM) dysfunction in the mouse brain. Importantly, I demonstrated that targeting blood-derived fibrinogen and limiting these protein deposits in the brain can slow WM disease, which has implications for the pathogenesis and treatment of human WM disease associated with AD and SVD (Montagne et al., Nature Medicine 2018). Last year, I showed that brain capillary disruption leads to rapid circulatory failure and neuronal loss via the loss of a specific capillary growth factor called pleiotrophin (Nikolakopoulou*, Montagne* et al., Nature Neuroscience 2019).

Between 2013 and 2015, I developed an advanced MRI method allowing detection of subtle vascular leakages in the living human brain (Montagne et al., Neuron 2015). I showed that subtle vascular breakdown during normal aging begins in the hippocampus, a region critical for learning and memory. Importantly, these vascular leakages worsen with cognitive decline. In a follow-up study, I also revealed that an accelerated vascular breakdown may contribute to cognitive impairment, independently of the classical AD amyloid and tau biomarkers (Nation*, Sweeney*, Montagne* et al., Nature Medicine 2019). Finally, I found that the gene variant APOE4, major genetic risk for AD, is linked to defects in the blood–brain barrier via activation of cyclophilin A and matrix metalloproteinase-9 in capillary pericytes, ultimately causing vascular disruption in brain regions involved in learning and memory (Montagne et al., Nature 2020).