ArticleActa neuropathologica communications2019
Blood brain barrier leakage is not a consistent feature of white matter lesions in CADASIL.
Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- Impairment of hippocampal gamma oscillations, mitochondria and neurovascular function in CADASIL.Brain : a journal of neurology · 2026Article
- Extracellular matrix remodelling in neurological diseases.Nature reviews. Neurology · 2026Review
- Shared neuropathological features of mild traumatic brain injury and anesthesia.Frontiers in neurology · 2026Review
- Assessment of Small Vessel Density Changes in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalophy (CADASIL) by High-Resolution Black-Blood MRI.Journal of magnetic resonance imaging : JMRI · 2026Article
- Restoring brain barriers: an innovative approach for treating neurological disorders.Fluids and barriers of the CNS · 2025Review
- The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025Review
- The pathogenesis of cerebral small vessel disease and vascular cognitive impairment.Physiological reviews · 2025Review
- The Pathobiology of Cerebrovascular Lesions in CADASIL Small Vessel Disease.Basic & clinical pharmacology & toxicology · 2025Review
- Cerebrovascular Function in Sporadic and Genetic Cerebral Small Vessel Disease.Annals of neurology · 2025Article
- Monogenic causes of cerebral small vessel disease- models for vascular cognitive impairment and dementia?Current opinion in psychiatry · 2025Review
- CADASIL: A NOTCH3-associated cerebral small vessel disease.Journal of advanced research · 2024Review
- Blended Phenotype ofNeurology. Genetics · 2024Article
- Heterogeneous blood-brain barrier dysfunction in cerebral small vessel diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Pathophysiology of cerebral small vessel disease: a journey through recent discoveries.The Journal of clinical investigation · 2024Review
- A multicenter, single-arm, phase II clinical trial of adrenomedullin in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.Cerebral circulation - cognition and behavior · 2024Article
- Most common NOTCH3 mutations causing CADASIL or CADASIL-like cerebral small vessel disease: A systematic review.Cerebral circulation - cognition and behavior · 2024Review
- IGF1R deficiency in vascular smooth muscle cells impairs myogenic autoregulation and cognition in mice.Frontiers in aging neuroscience · 2024Article
- Enlarged perivascular spaces are associated with white matter injury, cognition and inflammation in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.Brain communications · 2024Article
- Diffusion prepared pseudo-continuous arterial spin labeling reveals blood-brain barrier dysfunction in patients with CADASIL.European radiology · 2023Article
- Neuropathology of microbleeds in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).Journal of neuropathology and experimental neurology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic paradigm of small vessel disease (SVD) caused by NOTCH3 mutations that stereotypically lead to the vascular accumulation of NOTCH3 around smooth muscle cells and pericytes. White matter (WM) lesions (WMLs) are the earliest and most frequent abnormalities, and can be associated with lacunar infarcts and enlarged perivascular spaces (ePVS). The prevailing view is that blood brain barrier (BBB) leakage, possibly mediated by pericyte deficiency, plays a pivotal role in the formation of WMLs. Herein, we investigated the involvement of BBB leakage and pericyte loss in CADASIL WMLs. Using post-mortem brain tissue from 12 CADASIL patients and 10 age-matched controls, we found that WMLs are heterogeneous, and that BBB leakage reflects the heterogeneity. Specifically, while fibrinogen extravasation was significantly increased in WMLs surrounding ePVS and lacunes, levels of fibrinogen leakage were comparable in WMLs without other pathology ("pure" WMLs) to those seen in the normal appearing WM of patients and controls. In a mouse model of CADASIL, which develops WMLs but no lacunes or ePVS, we detected no extravasation of endogenous fibrinogen, nor of injected small or large tracers in WMLs. Moreover, there was no evidence of pericyte coverage modification in any type of WML in either CADASIL patients or mice. These data together indicate that WMLs in CADASIL encompass distinct classes of WM changes and argue against the prevailing hypothesis that pericyte coverage loss and BBB leakage are the primary drivers of WMLs. Our results also have important implications for the interpretation of studies on the BBB in living patients, which may misinterpret evidence of BBB leakage within WM hyperintensities as suggesting a BBB related mechanism for all WMLs, when in fact this may only apply to a subset of these lesions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.