Dr Axel Montagne

Chancellor's Fellow & UK DRI Group Leader

Background

My name is Axel Montagne, I completed my PhD at the University of Caen Normandy (France) with Professor Denis Vivien in 2012, followed by a postdoctoral training at the University of Southern California (USA) with Professor Berislav Zlokovic from 2013 to 2020. I published several articles about the vascular contribution to dementia in humans but also using innovative animal models. In December 2020, I have joined the University of Edinburgh Centre for Clinical Brain Sciences as a Chancellor’s fellow. I combine molecular approaches with rodent non-invasive imaging, particularly MRI and PET, to study the causes and effects of blood-brain barrier (BBB) dysfunction in the context of neurodegenerative disease. BBB dysfunction is a major cause of inflammatory and bioenergetic deregulation in the brain, but the interplay between pericytes and endothelial cells that causes this collapse is not fully delineated. My lab is now focusing on probing BBB function and pericyte-endothelial cross-talk, especially the consequences of pericyte dysfunction on endothelial cells and the BBB, plus reciprocal signaling by activated endothelial cells.

Research summary

Our brain is an energy-hungry organ surrounded by a rich network of blood vessels supplying the oxygen and nutrients required to function. It is essential that the microenvironment in the brain is finely controlled, and this is achieved through the specialist blood-brain-barrier (BBB) structure. However, dysfunction of the BBB is recognised as one of the earliest events in the progression of brain disorders that cause dementia, and scientists are working to understand why this occurs.

I have previously discovered that one type of cell within the BBB, the pericyte, is particularly affected during disease and I aim to fully understand the consequences to the BBB and brain health as a whole. Using a combination of advanced molecular and imaging techniques including MRI, I seek to uncover the disease mechanisms at play and identify therapeutic targets for intervention

Affiliated research centres

Project activity

With the role of pericytes in brain disorders established, fundamental mechanistic insights must now be uncovered. Questions still remain as to what can cause pericytes to become dysfunctional and ultimately die, and how pericyte loss in turn destabilises the endothelial cells lining the BBB. To address these questions, I will exploit my expertise in vascular biology, PET/MR, and optical imaging, and collaborate with local rexperts in transcriptomic analyses and in vitro systems. Greater knowledge in these areas may lead to novel therapeutic targets for cerebrovascular stabilisation in chronic neurodegenerative disease.

Current project grants

- UK DRI Strategic Capacity Building Award
Dates of Award: 15/12/20-14/12/25
- Grant No. (PI): A2019279S (Bonnin, Montagne)
Dates of Award: 07/01/19-06/30/22
Agency: BrightFocus Foundation
Title: Prenatal disruption of blood-placenta/brain barrier formation programs AD risk later in life
Description: The goal of this project is to uncover the cellular and molecular mechanisms by which inflammation disrupts blood-brain barrier (BBB) formation and function during and after pregnancy, leading to Alzheimer’s disease (AD)-like phenotypes in the adult offspring.

Past project grants

- Grant No. (PI): 007851-00001 (Montagne)
Dates of Award: 09/01/19-12/31/20
Agency: Fondation Leducq Transatlantic Network of Excellence “Perivascular Spaces in Small Vessel Disease"
Title: White matter endothelial dysfunction in a SVD-relevant mouse model of pericyte deficiency
Description: Pilot project to investigate the possible association between endothelial dysfunction and SVD-related white matter changes in pericyte-deficient mice.

- Grant No. (PI): 5P50AG005142-35 (Montagne)
Dates of Award: 04/01/19-03/31/21
Agency: NIH/NIA
Title: Molecular magnetic resonance imaging of the inflamed blood-brain barrier in normal aging and Alzheimer’s disease
Description: Pilot project to study cerebrovascular inflammation during normal aging and AD progression using cutting-edge micro-PET-MRI techniques.

- Grant No. (PI): 0000 (Montagne)
Dates of Award: 02/27/19-01/20/21
Agency: USC Mark & Mary Stevens Neuroimaging and Informatics Institute
Title: Imaging of blood-brain barrier permeability at 7T MRI in humans
Description: Pilot project to optimize brain dynamic contrast-enhanced MRI sequence and imaging post-processing at 7T in humans and to test/confirm regional blood-brain barrier permeability changes during normal aging and cognitive dysfunction.

In the press

  1. Commentary on Saridin et al. Brain amyloid β, cerebral small vessel disease and cognition: A memory clinic study. Neurology. 2020;10.1212/WNL.0000000000011029. https://journals.lww.com/neurotodayonline/Fulltext/2020/11050/Alzheimer_s_and_Cerebral_Small_Vessel_Disease.4.aspx.
  2. Dr. Axel Montagne, Associate Professor of Research Physiology & Neuroscience, weighs in on whether the dementia gene could increase risk of COVID-19: https://www.beingpatient.com/apoe4-dementia-gene-covid19-risk/?fbclid=IwAR3-G42ur1zA_s_4-LF8j74Mf4KgkLg2Y760dOADh6bjKkWXmLwZ9i_qva4.
  3. Facebook Live discussing “Alzheimer's, Inflammation, and Covid-19” with Drs. Axel Montagne and Caleb Finch, organized by Leigh Hopper (Media Relations Specialist at the University of Southern California), June 24th, 2020 (https://www.facebook.com/usc/videos/2523996221245126).
  4. “ISTAART Journal Club: Meet the Author webinar”. Montagne et al., Nature 2020 “APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline” was selected by Dr. Ozama Ismail (OHSU). Q&A with Drs. Axel Montagne and Berislav Zlokovic.
  5. ApoE4 damages protective barrier of the brain. https://www.beingpatient.com/apoe4-damages-protective-barrier-of-the-brain/?fbclid=IwAR1hw0cbVT74S2qxybC4l9zuwquMvpkypZayDgQ-CFYyEO1opkFPtI15S1Q.
  6. Alzheimer’s gene triggers early breakdowns in blood-brain barrier, predicting cognitive decline. https://news.usc.edu/169420/alzheimers-gene-apoe4-blood-brain-barrier-cognitive-decline-usc-research. Published 04/29/2020.
  7. Half of all dementias, including Alzheimer’s, start with damaged ‘gatekeeper cells’.https://news.usc.edu/135765/half-of-all-dementias-start-with-damaged-gatekeeper-cells. Published 02/05/2018.
  8. Montagne A. Video abstract: Blood-Brain Barrier Breakdown and Cognitive Impairment in Humans (CellPress). From Montagne’s article, Neuron. 85:296-302, 2015. PMID: 25611508, PMCID: PMC4350773. (http://www.cell.com/cms/attachment/2041269709/2055112227/mmc3.mp4).
  9. Scans detect aging brain issues linked to dementia. http://news.usc.edu/74051/usc-scientists-find-possible-prevent-of-alzheimers-and-dementia. Published 01/21/2015.