ArticleBrain pathology (Zurich, Switzerland)2018
Severe white matter astrocytopathy in CADASIL.
Article in Brain pathology (Zurich, Switzerland), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 51 citations in OpenAlex.
- Cognitive Decline, Neurologic Involvement, and Neonatal Crisis inNeurology. Genetics · 2026Article
- Diagnostic Value and Clinical Significance of Temporopolar White-Matter Hyperintensities in CADASIL and Sporadic Small-Vessel Disease.Journal of clinical neurology (Seoul, Korea) · 2026Article
- Biomarker advancements in cerebral small vessel disease: An overview.Neural regeneration research · 2026Article
- NOTCH3 CADASIL Variant Receptor Aggregation Requires NOTCH3 Wild-Type Receptors: Identification of Highly Selective Inhibitors That Block the Process.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- NOTCH3 Mutations in CADASIL: a multicellular perspective on neurodegeneration.Cell communication and signaling : CCS · 2026Review
- The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025Review
- Is migraine a common manifestation of CADASIL? Arguments Pros.The journal of headache and pain · 2025Article
- NOTCH3 Mutation Causes Glymphatic Impairment and Promotes Brain Senescence in CADASIL.CNS neuroscience & therapeutics · 2025Article
- Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Heterogeneous blood-brain barrier dysfunction in cerebral small vessel diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Regional differences in the link between water exchange rate across the blood-brain barrier and cognitive performance in normal aging.GeroScience · 2024Article
- Most common NOTCH3 mutations causing CADASIL or CADASIL-like cerebral small vessel disease: A systematic review.Cerebral circulation - cognition and behavior · 2024Review
- Diffusion prepared pseudo-continuous arterial spin labeling reveals blood-brain barrier dysfunction in patients with CADASIL.European radiology · 2023Article
- Decreased water exchange rate across blood-brain barrier in hereditary cerebral small vessel disease.Brain : a journal of neurology · 2023Article
- Review
- Neuropathology of microbleeds in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).Journal of neuropathology and experimental neurology · 2023Article
- Roles of NG2 Glia in Cerebral Small Vessel Disease.Neuroscience bulletin · 2023Review
- Postmortem 7T MRI for guided histopathology and evaluation of cerebrovascular disease.Journal of neuropathology and experimental neurology · 2022Article
- Differential perivascular microglial activation in the deep white matter in vascular dementia developed post-stroke.Brain pathology (Zurich, Switzerland) · 2022Article
- Evidence of beta amyloid independent small vessel disease in familial Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by strategic white matter (WM) hyperintensities on MRI. Pathological features include WM degeneration, arteriolosclerosis, lacunar infarcts, and the deposition of granular osmiophilic material. Based on the hypothesis that the gliovascular unit is compromised, we assessed the nature of astrocyte damage in the deep WM of CADASIL subjects.
methodsWe evaluated post-mortem brains from CADASIL, cerebral small vessel disease, similar age cognitively normal and older control subjects. Standard immunohistochemical, immunofluorescent, and unbiased stereological methods were used to evaluate the distribution of astrocytes, microvessels, and autophagy markers in five different brain regions.
resultsCompared to the controls, the deep WM of CADASIL subjects overall showed increased numbers of glial fibrillary acidic protein (GFAP)-positive clasmatodendritic astrocytes (P=0.037) and a decrease in the percentage of normal appearing astrocytes (P=0.025). In accord with confluent WM hyperintensities, the anterior temporal pole contained abundant clasmatodendritic astrocytes with displaced aquaporin 4 immunoreactivity. Remarkably, we also found strong evidence for the immunolocalization of autophagy markers including microtubule-associated protein 1, light chain 3 (LC3), and sequestosome 1/p62 and Caspase-3 in GFAP-positive clasmatodendritic cells, particularly within perivascular regions of the deep WM. LC3 was co-localized in more than 90% of the GFAP-positive clasmatodendrocytes.
conclusionsOur novel findings show astrocytes undergo autophagy-like cell death in CADASIL, with the anterior temporal pole being highly vulnerable. We propose astrocytes transform from normal appearing type A to hypertrophic type B and eventually to clasmatodendritic type C cells. These observations also suggest the gliovascular unit of the deep WM is severely impaired in CADASIL.
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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.