FoundMyFitness · 2023-02-28 · Rhonda Patrick (host), Axel Montagne

Axel Montagne, PhD, on Solving Alzheimer’s and Dementia with Blood-Brain Barrier Repair

74 research-tied claims examined: 5 contradicted 5 overstated 7 context 50 supported 7 unverified

Contradicted by research

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.

contradicts: Prevalence of mixed neuropathologies in age-related neurodegenerative diseases: A communit… (Alzheimer's & dementia : the journal of the Alzheimer's Association 2025) · cited 21x in the literature
"Alzheimer's disease neuropathological change (ADNC, 48%), Lewy body disease (LBD, 13%), and cerebrovascular disease (CVD, 63%) were also prevalent, often co-occurring with regional variations." (abstract, results, passage verified)
pubmed full study (doi)
contradicts: Effects of concurrent neuropathologies with Alzheimer disease neuropathologic change on co… (Journal of neuropathology and experimental neurology 2026)
"We examined cognitive changes associated with several neuropathologic entities, alone and in combination. We studied 808 participants from the National Alzheimer's Coordinating Center to assess associations between neuropathologic diagnoses (from autopsy) and neuropsychologic test scores... Neuropathologies included: Alzheimer disease neuropathologic change (ADNC), Lewy body disease (LBD), vascular brain injury (VBI), and limbic-predominant age-related TDP43 encephalopathy neuropathologic change (LATE-NC)." (abstract, methods, passage verified)
pubmed full study (doi)

0:22:39 Axel Montagnecontradictedmoderate

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.

contradicts: Neutrophil breaching of the blood vessel pericyte layer during diapedesis requires mast ce… (Nature communications 2022) · cited 37x in the literature
"Using confocal intravital microscopy, we observe directed abluminal neutrophil motility along pericyte processes towards perivascular MCs, a response that created neutrophil extravasation hotspots... MC-derived IL-17A regulates the enrichment of key effector molecules ICAM-1 and CXCL1 in nearby pericytes." (abstract, results)
pubmed full study (doi)

0:51:21 Axel Montagnecontradictedvery low

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.

partial: Pericyte degeneration causes white matter dysfunction in the mouse central nervous system. (Nature medicine 2018)RETRACTED · cited 364x in the literature
"Fibrinogen and fibrin fibrils initiated autophagy-dependent cell death in oligodendrocyte and pericyte cultures, whereas pharmacological and genetic manipulations of systemic fibrinogen levels in pericyte-deficient, but not control mice, influenced the degree of white-matter fibrin(ogen) deposition, pericyte degeneration, vascular pathology and white-matter changes." (abstract, results, passage verified)
pubmed full study (doi)
contradicts: Retraction Note: Pericyte degeneration causes white matter dysfunction in the mouse centra… (Nature medicine 2024)RETRACTED
"Retraction Note: Pericyte degeneration causes white matter dysfunction in the mouse central nervous system." (title, passage verified)
pubmed full study (doi)

0:58:15 Axel Montagnecontradictedvery low

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.

contradicts: Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelinati… (Frontiers in immunology 2021) · cited 33x in the literature
"Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white matter hypoperfusion (decreased CBF on DSC-MRI) and exacerbated the BBB permeability (extravascular IgG deposits) resulting from BCAS." (abstract, results, passage verified)
pubmed full study (doi)

0:46:13 Axel Montagnecontradictedvery low

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.

contradicts: Pericytes regulate vascular immune homeostasis in the CNS. (Proceedings of the National Academy of Sciences of the United States of America 2021) · cited 172x in the literature
"Additionally, administration of anti-VCAM-1 and anti-ICAM-1 antibodies reduces leukocyte infiltration and diminishes the severity of atypical EAE symptoms of Pdgfb ret/ret mice, indicating that the proinflammatory endothelium due to absence of pericytes facilitates exaggerated neuroinflammation." (abstract, results, passage verified)
pubmed full study (doi)

Unverified means no publication matching the claim was located; it does not prove the claim false. Spotted an error? See the corrections policy - disputes from the people quoted are prioritized.