HoldsUp

Axel Montagne

UK Dementia Research Institute at the University of Edinburgh Centre for Clinical Brain Sciences

Axel Montagne, PhD, is a Chancellor's Fellow and group leader at the UK Dementia Research Institute at the University of Edinburgh Centre for Clinical Brain Sciences. His research focuses on the role of brain vasculature and blood-brain barrier dysfunction in the early stages of dementia and age-related cognitive decline. His published studies cover topics including glial-vascular interactions, pericytes, transcriptomics of brain vascular cells, cerebral small vessel disease, and neurodegenerative mechanisms in Alzheimer's disease.

62 claims checked on air: 5 context 5 contradicted 3 overstated 43 supported 6 unverified

What they said on air - contradicted

14 citing their own research

0:02:40contradictedhighAxel Montagne, PhD, on Solving Alzheimer’s and Dementia with

Postmortem brain tissue from Alzheimer's disease patients consistently displays vascular pathology across every single case.

"there are many studies back from 20, 30 years ago that show that when you look at the postmortem brain sample and tissue, just the tissue of people that died from Alzheimer's disease, you can see a lot of vascular problems on every single case." (said at 0:02:40)

The speaker claims that postmortem brain tissue from Alzheimer's disease patients displays vascular pathology in "every single case" (100% of cases). While cerebrovascular pathology—such as microvascular lesions, infarcts, or cerebral amyloid angiopathy (CAA)—is highly prevalent in individuals with Alzheimer's disease and frequently co-occurs as a mixed pathology, neuropathological autopsy studies consistently demonstrate that it is not universal across all Alzheimer's cases. Large postmortem cohorts (e.g., PMID 39582417, PMID 42024684) show that vascular brain injury or cerebrovascular disease occurs in a significant subset of Alzheimer's decedents (e.g., 63% overall cerebrovascular disease in large brain bank studies), but not in 100% of cases. Pure Alzheimer's disease neuropathology without concomitant vascular lesions is well documented.

0:22:39contradictedmoderateAxel Montagne, PhD, on Solving Alzheimer’s and Dementia with

Endothelial inflammation causes brain pericytes to physically detach from cerebral vessels to allow immune cells to extravasate into brain tissue.

"the pericyte will have to detach because to let the immune cells go through physically, if the pericyte stays attached to the vessel, there is no possibility for the immune cells to go through and do their job." (said at 0:22:39)

The claim that pericytes must physically detach from cerebral vessels to allow immune cells to extravasate is contradicted by vascular and leukocyte trafficking studies. During leukocyte diapedesis and extravasation, pericytes remain adherent to the abluminal vessel wall rather than detaching to clear a physical opening. Extravasating leukocytes migrate along pericyte processes and navigate through pre-existing inter-pericyte gaps and exit portals, guided directly by adhesion molecules (such as ICAM-1) and chemoattractants expressed on the surface of intact, attached pericytes.

0:46:13contradictedvery lowAxel Montagne, PhD, on Solving Alzheimer’s and Dementia with

VCAM-1 plays a major role upstream of pericyte detachment in the cerebral microvasculature.

"and we know in the lab, we know that VCAM-1 plays a major role upstream of pericyte detachment." (said at 0:46:13)

The relationship described by the speaker is inverted. In neurovascular unit biology, pericyte loss or detachment occurs upstream of endothelial activation and vascular cell adhesion molecule-1 (VCAM-1) upregulation, not downstream of it. Brain capillary pericytes maintain endothelial quiescence; when pericytes detach or are genetically depleted (e.g., in Pdgfb-deficient models), the brain microvascular endothelium exhibits increased expression of VCAM-1 and ICAM-1, facilitating leukocyte infiltration and neuroinflammation. No published evidence demonstrates that VCAM-1 acts as an upstream trigger driving pericyte detachment.

0:51:21contradictedvery lowtheir own paperAxel Montagne, PhD, on Solving Alzheimer’s and Dementia with

Extravasated fibrinogen in the brain is neurotoxic and is internalized by oligodendrocytes, causing them to die via autophagy and promoting white matter disease.

"And we found that it's neurotoxic, so toxic to neurons. It's also toxic to oligodendrocytes... So they take it up, so they internalize fibrinogen, and they die by what we call autophagy, so it's almost like a suicide cell death, and which leads to white matter disease." (said at 0:51:21)

The claim refers to findings originally reported in a 2018 study (Montagne et al., Nature Medicine), which described pericyte degeneration leading to extravasated fibrinogen accumulation, autophagy-dependent cell death in oligodendrocytes, and white matter dysfunction in mouse models (PMID 29400711). However, this study was formally retracted in 2024 (PMID 38580816), invalidating its data and conclusions regarding fibrinogen-induced oligodendrocyte autophagy and white matter pathology.

0:58:15contradictedvery lowtheir own paperAxel Montagne, PhD, on Solving Alzheimer’s and Dementia with

Exposing mice to Los Angeles highway airborne particulate matter caused blood-brain barrier breakdown and pericyte degeneration within days.

"I'm part of two studies that we've published four to five years ago maybe where we expose the mice to airborne particles from Los Angeles. We were taking from the highway the particles and giving it to the mouse to see what's the impact of the pollution on vascular function... we found a high peak of vascular—it's a longitudinal disease, but very rapidly, a few days after giving the particles to the mouse, we were seeing blood-brain barrier breakdown and pericyte degeneration very quickly" (said at 0:58:15)

Published experimental research investigating the effects of Los Angeles traffic-derived nanoparticulate matter (nPM) in mice found that exposure to nPM alone did not alter blood-brain barrier integrity or regional cerebral blood flow. Instead, nPM exposure only exacerbated blood-brain barrier permeability and vascular pathology in the presence of pre-existing cerebral hypoperfusion induced by bilateral carotid artery stenosis.

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