The DOI matches its Crossref record; 176 of the 177 references it cites were found in a registry or an index.
Review: Molecular genetics and pathology of hereditary small vessel diseases of the brain
Abstract
Y. Yamamoto, L. Craggs, M. Baumann, H. Kalimo and R. N. Kalaria (2011) Neuropathology and Applied Neurobiology37, 94–113 Molecular genetics and pathology of hereditary small vessel diseases of the brain Advances in molecular genetics have enabled identification of several monogenic conditions involving small vessels predisposing to ischaemic and haemorrhagic strokes and diffuse white matter disease. With emphasis on cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), we review the molecular pathogenesis of recently characterized disorders including cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), retinal vasculopathy with cerebral leukodystrophy (RVCL) and the Collagen type IV, alpha 1 (COL4A1)‐related disorders. CADASIL remains the most common hereditary small vessel disease (SVD) caused by >190 different mutations in the NOTCH3 gene, which encodes a cell‐signalling receptor. Mutant NOTCH3 instigates degeneration of vascular smooth muscle cells in small arteries and arterioles leading to recurrent lacunar infarcts. Mutations in the serine protease HTRA1 gene are associated with CARASIL. Aberrant HTRA1 activity results in increased transforming growth factor‐β signalling provoking multiple actions including vascular fibrosis and extracellular matrix synthesis. The RVCL disorders characterized by profound retinopathy are associated with mutations in TREX1, which encodes an abundant 3′–5′ DNA‐specific exonuclease. TREX1 mutations lead to detrimental gain‐of‐function or insufficient quantities of enzyme. The COL4A1‐related disorders are highly variable comprising four major phenotypes with overlapping systemic and central nervous system features including SVD with cerebral haemorrhages in children and adults. Mutant COL4A1 likely disrupts the extracellular matrix resulting in fragile vessel walls. The hereditary SVDs albeit with variable phenotypes demonstrate how effects of different defective genes converge to produce the characteristic arteriopathy and microvascular disintegration leading to vascular cognitive impairment.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Multiple hemorrhages or hemorrhagic infarcts are often associated with VCD, the common causes being sporadic or hereditary conditions associated with cerebral amyloid angiopathy (CAA)64 and other genetic disorders,65 although hypertension may have a role.”
From Diagnostic Criteria for Vascular Cognitive Disorders: A VASCOG Statement (2014) · cites this paper as [65]
In the citing paper
“Multiple hemorrhages or hemorrhagic infarcts are often associated with VCD, the common causes being sporadic or hereditary conditions associated with cerebral amyloid angiopathy (CAA)64 and other genetic disorders,65 although hypertension may have a role.”
From Diagnostic Criteria for Vascular Cognitive Disorders: A VASCOG Statement (2014) · cites this paper as [65]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Notch Signaling: Cell Fate Control and Signal Integration in Development
Artavanis-Tsakonas, S., Rand, M. D., & Lake, R. J. (1999) · Science · doi:10.1126/science.284.5415.770 · Cited by 5,909
Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus
Shi, Y., & Massagué, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00432-x · Cited by 5,860
Pantoni, L. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70104-6 · Cited by 3,405
Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia
Joutel, A., Corpechot, C., Ducros, A., Vahedi, K., Chabriat, H., Mouton, P., Alamowitch, S., Domenga, V., Cécillion, M., Maréchal, E., et al. (1996) · Nature · doi:10.1038/383707a0 · Cited by 2,068
Massagué, J. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35043051 · Cited by 1,925
Trex1 prevents cell-intrinsic initiation of autoimmunity
Stetson, D. B., Ko, J. S., Heidmann, T., & Medzhitov, R. (2008) · Cell · doi:10.1016/j.cell.2008.06.032 · Cited by 1,280
Chabriat, H., Joutel, A., Dichgans, M., Tournier-Lasserve, E., & Bousser, M.-G. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70127-9 · Cited by 1,088
Extracellular control of TGFβ signalling in vascular development and disease
ten Dijke, P., & Arthur, H. M. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2262 · Cited by 813
A Variant of the HTRA1 Gene Increases Susceptibility to Age-Related Macular Degeneration
Yang, Z., Camp, N. J., Sun, H., Tong, Z., Gibbs, D., Cameron, D. J., Chen, H., Zhao, Y., Pearson, E., Li, X., et al. (2006) · Science · doi:10.1126/science.1133811 · Cited by 796
PI 3-kinase, Akt and cell survival
Downward, J. (2004) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2004.01.002 · Cited by 791
Research works printed but not linked: 3
- Kalimo H, 2005, Cerebrovascular Diseases, Pathology & Genetics, 324
- van Bogaert L, 1955, Encephalopathie sous‐corticale progressive (Binswanger) a evlution rapide chez duez soeurs, Med Hellen, 24, 961
- Colmant HJ, 1980, Familiäre zerebrale Gefässerkrankung, Zbl Allg Path, 124, 163
Cited by
Sorted by citations
Items 101–125 of 125
Newer Research and its Significance
Martin, V. T. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800901-7.00024-0 · Cited by 2
Systematic Genetic Assessment in Young Patients With Cryptogenic Stroke: The ES-EASY project
Mania-Pâris, L., Vitobello, A., Safraou, H., Mau‐Them, F. T., Duffourd, Y., Nambot, S., Bruel, A., Denommé‐Pichon, A., Duloquin, G., Béjot, Y., et al. (2025) · Stroke · doi:10.1161/strokeaha.125.051020 · Cited by 1
Multimodal neuroimaging of Col4a1-mutant mouse models of Gould syndrome
Gao, X., Wang, X., Labelle‐Dumais, C., Gould, D. B., & Chaumeil, M. M. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1639871 · Cited by 1
Rasooli, S., Moslemi, F., & Tagavi, S. (2014) · International Journal of Women s Health and Reproduction Sciences · doi:10.15296/ijwhr.2014.55 · Cited by 1
Other Monogenetic Stroke Disorders
Cole, J. W., & Miller, J. G. (2012) · Springer eBooks · doi:10.1007/978-0-85729-209-4_10 · Cited by 1
Not Described Variant of Notch3 Gen for Cadasil Disease
Mellinger, S., Romero, D., Visich, A., Chanampa, S., Ivetich, G., Burgos, M., & Orzuza, G. (2020) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2020.104803 · Cited by 1
CADASIL – obraz kliniczny, diagnostyka i leczenie
Dziewulska, D. (2011) · DOAJ (DOAJ: Directory of Open Access Journals) · Cited by 1
Pediatric Vascular Malformations
Magaki, S., Tashjian, R. S., & Vinters, H. V. (2018) · Wiley eBooks · doi:10.1002/9781119013112.ch24 · Cited by 1
Blood-Brain Barrier Permeability and Inflammation in Cerebral Small Vessel Disease
Walsh, J. (2019) · Apollo (University of Cambridge) · doi:10.17863/cam.50869 · Cited by 2
Morphometric Study of Cerebral Arterioles in CADASIL
Miao, Q. (2011) · UTUPub (University of Turku)
Bereczki, D., & Chabriat, H. (2012)
Hereditary cerebral small vessel disease and the role of genetic factors
Opherk, C., & Dichgans, M. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9781139382694.009
Diagnosis and management of uncommon and genetic cerebrovascular diseases
Ichord, R. (2012) · CRC Press eBooks · doi:10.3109/9781841848075-29
Ferrer, I. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9781107588660.017
Hamel, É. (2017) · Primer on Cerebrovascular Diseases · doi:10.1016/b978-0-12-803058-5.00066-7
de Paiva, A. R. B. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2019.tde-16102019-142301
Dysfunction of Glymphatic System Caused by Cerebral Small Vessel Disease
Uemura, M., & Onodera, O. (2019) · Nihon Naika Gakkai Zasshi · doi:10.2169/naika.108.582
The Hormone Replacement Therapy in Cerebrovascular Diseases: Is the Receptor Remodeled?
Wang, F. (2013) · Science Insights · doi:10.15354/si.13.re001
Other Monogenetic Stroke Disorders
Cole, J. W., & Stack, C. A. (2017) · Springer eBooks · doi:10.1007/978-3-319-56210-0_10
Diagnosis and management of uncommon and genetic cerebrovascular diseases
Ichord, R. (2012) · Informa Healthcare eBooks · doi:10.3109/9781841848075.026
Schröder, H., de Vos, R. A. I., Huggenberger, S., Müller-Thomsen, L., Rozemüller, A. J. M., Hedayat, F., & Moser, N. (2023) · Springer eBooks · doi:10.1007/978-3-030-89980-6_1
Other Monogenetic Stroke Disorders
Stack, C. A., & Cole, J. W. (2024) · Springer eBooks · doi:10.1007/978-3-031-41777-1_8
Systematic Review and Phenome‐Wide Scans of Genetic Associations with Vascular Cognitive Impairment
Diany, R., & Taliun, S. A. G. (2024) · Advanced Biology · doi:10.1002/adbi.202300692
Small vessel disease: what it is and how to assess it
Humphreys, C. A., & Smith, C. T. (2026) · Diagnostic histopathology · doi:10.1016/j.mpdhp.2026.03.001
Metadata
- Authors
- Yamamoto, Y., Craggs, L., Baumann, M., Kalimo, H., & Kalaria, R. N.
- Affiliations
- Newcastle University (GB)
- University of Helsinki (FI)
- Corresponding author
- Kalaria, R. N.
- Venue
- Neuropathology and Applied Neurobiology
- Publisher
- Wiley
- Published
- 2011-01-11
- Volume
- 37
- Issue
- 1
- Pages
- 94-113
- ISSN
- 0305-1846 (ISSN-L)
- 1365-2990
- OpenAlex
- W1934351417
- Cited by
- 125
- References
- 177
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 11 · 2018: 9 · 2017: 8 · 2016: 10 · 2015: 10 · 2014: 17 · 2013: 7 · 2012: 15
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropathology and Applied Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- National Institute of Neurological Disorders and Stroke (R21NS054047, NS054047)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Cerebrovascular and genetic disorders
- Health Sciences › Medicine › Clinical Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- CADASIL, CARASIL, NOTCH3 mutations, HTRA1, TREX1, COL4A1, lacunar infarction, cerebral hemorrhage, white matter disease, vascular cognitive impairment, transforming growth factor-beta signalling, extracellular matrix
- MeSH terms
- Receptor, Notch3, Animals, Brain, Capillaries, Cerebral Arterial Diseases, Cerebral Infarction, Cerebrovascular Disorders, Humans, Molecular Biology, Mutation, Retinal Vessels, Signal Transduction, Collagen Type IV, CADASIL, Receptors, Notch, Leukoencephalopathies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
