Dr Axel Montagne
Senior Lecturer & UK DRI Group Leader
- Institute for Neuroscience and Cardiovascular Research (INCR), Centre for Clinical Brain Sciences (CCBS)
- UK Dementia Research Institute
Contact details
- Tel: 07895 730745
- Email: axel.montagne@ed.ac.uk
Address
- Street
-
49 Little France Crescent
- City
- Edinburgh
- Post code
- EH16 4SB
Background
Axel Montagne completed his PhD at the University of Caen Normandy (France) and undertook postdoctoral training at the University of Southern California (USA). He joined the University of Edinburgh in 2020 as a Chancellor’s Fellow and UK DRI Group Leader, and since 2025 is a Senior Lecturer and Group Leader within the BHF-UK DRI Centre for Vascular Dementia Research. His research focuses on the vascular contribution to dementia, combining molecular approaches with advanced imaging in animal models to understand how blood-brain barrier dysfunction arises. His lab studies how interactions between pericytes and endothelial cells maintain microvascular integrity, and how disruption of this crosstalk contributes to neurodegeneration.
Open to PhD supervision enquiries?
Yes
Current PhD students supervised
Daniela Jaime Garcia, Wellcome Trust Translational Neuroscience PhD Student
Dorota Stefancova, PhD Student
Krystal Laing, Wellcome Trust Translational Neuroscience PhD Student
Research summary
Blood-brain barrier (BBB) dysfunction is increasingly recognised as an early contributor to neurological disorders such as cerebral small vessel disease (cSVD) and Alzheimer’s disease (AD). My research focuses on the brain microvasculature, particularly the role of pericytes - specialised mural cells that regulate vascular stability, cerebral blood flow, immune cell trafficking, and BBB integrity.
My work in humans has provided evidence that BBB breakdown occurs early in ageing and cognitive decline, particularly in the hippocampus, and is closely linked to pericyte injury. We have also shown that BBB disruption is associated with APOE ε4, a major genetic risk factor for Alzheimer’s disease, and can predict cognitive impairment.
Using experimental models, my laboratory investigates the mechanisms by which pericyte dysfunction destabilises the cerebral microvasculature. Our studies demonstrate that pericyte loss can trigger capillary damage, white matter injury, and neurodegeneration through vascular and blood-derived toxic mechanisms.
Current work in the lab aims to define the molecular signals that regulate pericyte–endothelial communication and to identify pathways that could be targeted to stabilise the brain vasculature in neurodegenerative disease.
Current research interests
Our research aims to understand how cerebrovascular dysfunction contributes to neurodegeneration and dementia in order to identify new therapeutic targets. We combine molecular approaches with advanced imaging in experimental models, including MRI and microscopy, to investigate the causes and consequences of blood-brain barrier (BBB) dysfunction in ageing and neurodegenerative disease. A central focus of the lab is the interaction between pericytes and endothelial cells that maintain microvascular stability. Disruption of this crosstalk is increasingly recognised as a key driver of vascular dysfunction, inflammation, and metabolic imbalance in the brain. Using genetic mouse models of pericyte ablation, AAV-based approaches to induce endothelial dysfunction, and models of cerebral amyloidosis, we study how vascular injury develops and propagates across the neurovascular unit. We are particularly interested in the heterogeneity of pericyte and endothelial subpopulations along the arteriovenous axis and how these specialised vascular cells change during ageing and disease. Ultimately, our goal is to identify mechanisms and therapeutic strategies that preserve BBB integrity and vascular function in cerebral small vessel disease and Alzheimer’s disease.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
- MRC Career Development Award (CDA)
Dates of Award: 01/01/22-31/12/26
Agency: Medical Research Council
Title: Interplay between brain endothelial cells and pericytes in brain health and disease
- UK DRI Strategic Capacity Building Award
Dates of Award: 15/12/20-14/12/25
Agency: UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK
Title: Cerebrovascular and inflamm-ageing link to neurodegeneration and dementia
- 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
- 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.
- 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.
- 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).
- “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.
- ApoE4 damages protective barrier of the brain. https://www.beingpatient.com/apoe4-damages-protective-barrier-of-the-brain/?fbclid=IwAR1hw0cbVT74S2qxybC4l9zuwquMvpkypZayDgQ-CFYyEO1opkFPtI15S1Q.
- 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.
- 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.
- 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).
- 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.