The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index; none of the 21 sources its claims cite is checked for support yet.
Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL)
Open accessAbstract
OBJECTIVE: To characterize the clinical and MRI features of 2 families with adult-onset dominant leukoencephalopathy and strokes and identify the underlying genetic cause. METHODS: We applied MRI pattern recognition, whole-exome sequencing, and neuropathology. RESULTS: Based on brain imaging, 13 family members of 40 years or older from 2 families were diagnosed with the disease; in 11 family members of the same age, MRI was normal. In the affected family members, MRI showed a leukoencephalopathy that was disproportionately severe compared to the clinical disease. The clinical picture was dominated by ischemic and hemorrhagic strokes, slow and late cognitive deterioration, and therapy-resistant hypertension. With whole-exome sequencing, we identified one variant shared by both families and segregating with the disease: c.973C>T in CTSA. Haplotype analysis revealed a shared 1,145-kb interval encompassing the CTSA variant on chromosome 20q13.12, suggesting a common ancestor. Brain autopsy of 3 patients showed a leukoencephalopathy that was disproportionately extensive compared to the vascular abnormalities. CTSA encodes cathepsin A. Recessive CTSA mutations cause galactosialidosis. One of the numerous cathepsin A functions is to degrade endothelin-1. In the patients, striking endothelin-1 immunoreactivity was found in white matter astrocytes, correlating with increased numbers of premyelinating oligodendrocyte progenitors. This finding supports a role for endothelin-1 in the leukoencephalopathy through inhibition of oligodendrocyte progenitor maturation. CONCLUSIONS: CARASAL (cathepsin A-related arteriopathy with strokes and leukoencephalopathy) is a novel hereditary adult-onset cerebral small vessel disease. It is of interest that, next to the cerebral vascular abnormalities, endothelin-1 may have a role in the pathogenesis of the extensive leukoencephalopathy.
Overview
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Written from the paper’s full text.
TL;DR
CARASAL is a novel adult-onset autosomal dominant cerebral small vessel disease caused by a heterozygous CTSA variant, characterized by leukoencephalopathy, ischemic and hemorrhagic strokes, therapy-resistant hypertension, and late cognitive decline. The authors propose that cathepsin A dysfunction leads to endothelin-1 accumulation, which may impair oligodendrocyte progenitor maturation and contribute to the extensive white matter disease.
Key findings
- In 2 Dutch families, 13 individuals ≥40 years had MRI-defined disease (11 in F1, 2 in F2), while 11 F1 members ≥40 years had normal MRI; MRI showed frontoparietal periventricular/deep white matter leukoencephalopathy that was disproportionately severe compared with clinical disease, with relative temporal white matter sparing.
- Whole-exome sequencing identified a heterozygous CTSA variant, c.973C>T p.(Arg325Cys), shared by both families and segregating with disease; two-point linkage in F1 gave a maximal LOD score of 5.4953 at theta 0, and haplotype analysis identified a shared 1,145-kb interval on chromosome 20q13.12 containing CTSA but not TTPAL.
- Neuropathology showed extensive leukoencephalopathy with myelin pallor, relatively preserved axons, astrogliosis, and unusual asymmetric fibrous thickening and near-total occlusion of distal arterioles; sclerotic index was more severe in patients (mean 0.55) than in sporadic SVD (mean 0.33) or normal controls (mean 0.27).
- In noninfarcted white matter, patients had increased premyelinating oligodendrocyte progenitor cells compared with sporadic SVD (p<0.05) and nonneurologic controls (p<0.01), lower myelin basic protein, increased CathA 54-kDa precursor, and strikingly increased endothelin-1 immunoreactivity in white matter astrocytes.
Methods
- Clinical and imaging study of 2 Caucasian Dutch families: F1 included 22 members ≥40 years (11 affected, 11 unaffected by MRI), and F2 included 2 affected patients; MRI pattern recognition was used to classify disease.
- Genetic analysis used whole-exome sequencing in 3 F1 members (2 affected, 1 unaffected), Sanger sequencing of CTSA and TTPAL, two-point linkage analysis, and microsatellite haplotype analysis around chromosome 20q13.12.
- Neuropathology included brain autopsy in 3 patients, body autopsy in 1, immunohistochemistry for CathA, GFAP, endothelin-1, β-amyloid, phosphorylated tau, Olig2, and PDGFRα, electron microscopy, Western blotting/SDS-PAGE, sclerotic index quantification, and leukocyte enzyme activity assays for carboxypeptidase, β-galactosidase, and neuraminidase-1.
Limitations
- The paper states that the possible functional role of the CTSA mutation in CARASAL is presently unexplained; nonreducing SDS-PAGE did not support misfolding of mutant CathA, and reduced CathA carboxypeptidase activity was not found in leukocytes.
- The authors state that further studies should determine whether only the p.(Arg325Cys) CTSA variant is associated with CARASAL or whether other mutations also increase small vessel disease risk.
- Evident limitations include the very small sample (2 families, 3 autopsied patients), limited F2 availability, and reliance on postmortem and immunohistochemical associations rather than direct functional proof that endothelin-1 accumulation causes the leukoencephalopathy.
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Claims the paper makes
52 Own result · 16 Sources not found · 13 Own interpretation · 2 Own method · 1 No basis given
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Haplotype analysis revealed a shared 1,145-kb interval encompassing the CTSA variant on chromosome 20q13.12,suggesting a common ancestor.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > Abstract
plaincorrelationaln = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the affected family members, MRI showed a leukoencephalopathy that was disproportionately severe compared to the clinical disease.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > Abstract
plaincorrelationaln = 13- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The MRI pattern was characterized by signal changes in the frontoparietal periventricular and deep white matter that were patchy in younger patients (figure 1, A-H) and became diffuse with increasing age (figure 1, I-L).”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Seven patients had infarcts in basal nuclei, brainstem, cerebellum, or cerebral hemispheres (figure 1, M and N).”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
plainn = 7- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All unaffected individuals had a normal brain MRI.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“With wholeexome sequencing, we identified one variant shared by both families and segregating with the disease: c.973C.T in CTSA.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > Abstract
plaincorrelationaln = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Brain autopsy of 3 patients showed a leukoencephalopathy that was disproportionately extensive compared to the vascular abnormalities.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > Abstract
plaincorrelationaln = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two-point linkage analysis for the CTSA variant in F1 showed a maximal logarithm of odds score of 5.4953 at theta 0 for the variant.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, under all conditions, the CathA 54-kDa precursor protein was increased in patients with CTSA mutation compared to neurologic and nonneurologic controls.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > CathA and ET-1 protein immunoreactivity in the brain.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“WES revealed no other dominant variants in this region”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
plainn = 2- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 19
- Probably not a substantial claim. 10
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the patients, striking endothelin-1 immunoreactivity was found in white matter astrocytes, correlating with increased numbers of premyelinating oligodendrocyte progenitors.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > Abstract
plaincorrelationaln = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on brain imaging, 13 family members of 40 years or older from 2 families were diagnosed with the disease; in 11 family members of the same age, MRI was normal.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > Abstract
plainn = 13- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Three patients had microbleeds and one had a small hemorrhage (figure 1P).”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
plainn = 3- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The temporal white matter was relatively spared and the temporal poles were not affected.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The clinical picture was dominated by ischemic and hemorrhagic strokes, slow and late cognitive deterioration, and therapy-resistant hypertension.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > Abstract
plainn = 13- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“White matter pathology in CARASAL shows paucity of myelin, astrogliosis, and increased OPC numbers extending beyond the ischemic pathology, also present in patient F1-IV8 who had no infarcts and few lacunae.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In our patients, CathA-expressing astrocytes were spread over the white matter, whereas in capillary CAA, CADASIL, and sporadic SVD, they only clustered around infarcts.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Only the same heterozygous CTSA variant was found in patient F2-2 and her father, leaving CTSA as the only shared candidate gene.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In CARASAL, ET-1 overexpression coincides with increased numbers of premyelinating OPCs, decreased MBP amounts, and abundance of axons without myelin”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The CathA-positive cells have the morphology of astrocytes and express the astrocyte-specific marker GFAP (inset in A, GFAP in red and CathA in green).”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NOTCH3 sequencing was unrevealing and WES showed no known or possible pathogenic variants in COL4A1, COL4A2, TREX1, and CAA-related genes,”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“WES in 3 family members of F1, 2 affected and 1 unaffected, revealed 2 heterozygous candidate variants in 2 genes: c.973C.T, p.(Arg325Cys) in CTSA and c.544G.A, p.(Gly182Arg) in TTPAL, both located on chromosome 20q13.12(table 1).”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of note, in patients with CTSA mutation but not in the neurologic and nonneurologic controls, we detected unusual changes involving distal arteriolar branches, consisting of vessel wall fibrous thickening, which was remarkably asymmetric, and loss of smooth muscle cells with near-total occlusion of the lumen.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Using 13 consecutive microsatellite markers, we identified among F1 patients a shared haplotype of 8 consecutive markers flanked by markers D20S46 and D20S891 (physical genomic location Hg19 chr20: 41334729-45929596) (not shown), which was not shared by any of the unaffected F1 individuals.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the noninfarcted cerebral white matter, OPC numbers were higher in patients with CTSA mutation than in sporadic SVD (p , 0.05), and in both compared to nonneurologic controls (p , 0.01 and p , 0.001, respectively) (figure 3H).”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Most patients had signs of vascular disease with hypertension requiring multiple drugs, strokes, and TIAs.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“EM showed no granular osmiophilic material, basal lamina fragmentation or multilamination, or amyloid deposition in blood vessels, as seen in CADASIL, defects of collagen IVA1 and IVA2, TREX1-related disease, and CAA, respectively.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
plainn = 2- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Recessive CTSA mutations cause galactosialidosis due to deficiency of b-galactosidase and neuraminidase-1.30,31”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
What the sources say
- Not matchedcites [30]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [31]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Findings in multiple sclerosis indicate that astrocyte-derived ET-1 may inhibit OPC maturation.22”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
What the sources say
- Not matchedcites [22]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“ET-1 is a peptide degraded by CathA that has roles in vasoconstriction and OPC maturation.21,22”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > CathA and ET-1 protein immunoreactivity in the brain.
What the sources say
- Not matchedcites [21]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [22]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The lower panel confirms equal protein loading (GAPDH) (I).”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, since galactosialidosis is rare and hypertension and hypertension-related white matter lesions are common, such association may have easily been overlooked.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
hedgedSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Rests on an assumption: Parents of patients with galactosialidosis, who are obligatory CTSA mutation carriers, are not known to have increased risk of hypertension and SVD.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Similar oversights have occurred before.38,39”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
What the sources say
- Not matchedcites [38]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [39]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“CathA is synthesized as a single-chain precursor of 54 kDa that is converted into a catalytically active heterodimer consisting of 20-and 32-kDa subunits.28,29”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
What the sources say
- Not matchedcites [28]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [29]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Only recently it has become clear that heterozygous carriers of GBA1 mutations have an increased risk of Parkinson disease and Lewy body dementia.38”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
What the sources say
- Not matchedcites [38]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“The pathomechanism of SVD-related leukoencephalopathy is complex, also involving chronic hypoperfusion and hypoxia.32”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
What the sources say
- Not matchedcites [32]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Leukoencephalopathy is part of the general SVD histopathology phenotype, with loss of oligodendrocytes, myelin, and axons centered on abnormal vessels.32”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
What the sources say
- Not matchedcites [32]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
The paper relies on this without support.
Family members aged 40 years or older with a normal brain MRI are unaffected by the disease.
“Family members younger than 40 years without MRI or with normal MRI were considered to have unknown status and were excluded; 22 family members of 40 years or older were included.Based on MRI, 11 were diagnosed with vascular leukoencephalopathy and 11 were unaffected.”
The paper relies on this without support.
Heterozygous CTSA mutations have not been associated with disease.
“Heterozygous CTSA mutations have hitherto not been associated with disease.”
The paper relies on this without support.
The functional role of the CTSA mutation in CARASAL is unexplained.
“The possible functional role of the CTSA mutation in CARASAL is presently unexplained.”
The paper relies on this without support.
Parents of patients with galactosialidosis, who are obligatory CTSA mutation carriers, are not known to have increased risk of hypertension and SVD.
“Parents of patients with galactosialidosis, who are obligatory CTSA mutation carriers, are not known to have increased risk of hypertension and SVD.”
The paper relies on this without support.
Gaucher disease is caused by recessive mutations in GBA1, encoding glucocerebrosidase.
“It is long known that Gaucher disease is caused by recessive mutations in GBA1, encoding glucocerebrosidase.”
The paper relies on this without support.
Mature CathA is mainly found in lysosomes, where it stabilizes a multienzyme complex with b-galactosidase and neuraminidase-1.
“Mature CathA is mainly found in lysosomes, where it stabilizes a multienzyme complex with b-galactosidase and neuraminidase-1.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > Microsatellite marker analysis.
“the sclerotic index, which is the ratio of lumen diameter/external diameter, representing the degree of lumen narrowing”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
“Calculation of the sclerotic index revealed more severe lumen narrowing in our patients (mean 0.55) than in sporadic SVD (mean 0.33) and normal controls (mean 0.27).”
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
“patient F1-IV8 who had no infarcts and few lacunae”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
“DWI of patient F1-IV8 (53 years) (O)”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > Microsatellite marker analysis.
“Patient F1-IV8 also underwent body autopsy.”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
“Body autopsy of patient F1-V8 revealed atherosclerosis in the aorta and larger arteries”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > RESULTS
“c.973C.T, p.(Arg325Cys) in CTSA”
§ Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) > DISCUSSION
“CTSA | c.922C.T Arg308Cys Missense 20q13 | Up to C elegans Damaging | Not present | Yes | | | |”
Citations
Cites
The metabolic and molecular bases of inherited disease
Chen, Y.-T. (2001) · Medical Entomology and Zoology · Cited by 6,928
Wardlaw, J. M., Smith, E. E., Biessels, G. J., Cordonnier, C., Fazekas, F., Frayne, R., Lindley, R. I., O'Brien, J. T., Barkhof, F., Benavente, O. R., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70124-8 · Cited by 5,544
Montine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0910-3 · Cited by 2,894
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
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
Subcortical ischaemic vascular dementia
Román, G. C., Erkinjuntti, T., Wallin, A., Pantoni, L., & Chui, H. C. (2002) · The Lancet Neurology · doi:10.1016/s1474-4422(02)00190-4 · Cited by 1,067
Disulphide bridges in globular proteins.
Thornton, J. (1981) · Journal of Molecular Biology · doi:10.1016/0022-2836(81)90515-5 · Cited by 715
Francioli, L. C., Menelaou, A., Pulit, S. L., Elbers, C. C., Kloosterman, W. P., van Setten, J., Nijman, I. J., Renkens, I., de Bakker, P. I. W., van Dijk, F., et al. (2014) · Nature Genetics · doi:10.1038/ng.3021 · Cited by 651
Role of COL4A1 in Small-Vessel Disease and Hemorrhagic Stroke
Gould, D. B., Phalan, F. C., van Mil, S. E., Sundberg, J. P., Vahedi, K., Massin, P., Bousser, M. G., Heutink, P., Miner, J. H., Tournier-Lasserve, E., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa053727 · Cited by 581
Association of HTRA1 Mutations and Familial Ischemic Cerebral Small-Vessel Disease
Hara, K., Shiga, A., Fukutake, T., Nozaki, H., Miyashita, A., Yokoseki, A., Kawata, H., Koyama, A., Arima, K., Takahashi, T., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0801560 · Cited by 460
Richards, A., van den Maagdenberg, A. M. J. M., Jen, J. C., Kavanagh, D., Bertram, P. G., Spitzer, D., Liszewski, M. K., Barilla-LaBarca, M.-L., Terwindt, G. M., Kasai, Y., et al. (2007) · Nature Genetics · doi:10.1038/ng2082 · Cited by 441
COL4A1 Mutations and Hereditary Angiopathy, Nephropathy, Aneurysms, and Muscle Cramps
Plaisier, E. M., Gribouval, O., Alamowitch, S., Mougenot, B., Prost‐Squarcioni, C., Verpont, M. C., Marro, B., Desmettre, T. J., Cohen, S. Y., Roullet, E., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa071906 · Cited by 382
Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies
Révész, T., Holton, J. L., Lashley, T., Plant, G. T., Frangione, B., Rostagno, A. A., & Ghiso, J. A. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0501-8 · Cited by 300
Dementia, stroke, and vascular risk factors; a review
Sahathevan, R., Brodtmann, A., & Donnan, G. A. (2012) · International Journal of Stroke · doi:10.1111/j.1747-4949.2011.00731.x · Cited by 230
HeterozygousHTRA1mutations are associated with autosomal dominant cerebral small vessel disease
Verdura, E., Hervé, D., Scharrer, E. M., Amador, M. D. M., Guyant‐Maréchal, L., Philippi, A., Corlobé, A., Bergametti, F., Gazal, S., Prieto-Morin, C., et al. (2015) · Brain · doi:10.1093/brain/awv155 · Cited by 211
Astrocyte-derived endothelin-1 inhibits remyelination through notch activation
Hammond, T. R., Gadea, A., Dupree, J., Kerninon, C., Nait-Oumesmar, B., Aguirre, A., & Gallo, V. (2014) · Neuron · doi:10.1016/j.neuron.2013.11.015 · Cited by 206
Tikka, S., Baumann, M., Siitonen, M., Pasanen, P., Pöyhönen, M., Myllykangas, L., Viitanen, M., Fukutake, T., Cognat, E., Joutel, A., et al. (2014) · Brain Pathology · doi:10.1111/bpa.12181 · Cited by 189
The enigma of vascular cognitive disorder and vascular dementia
Jellinger, K. A. (2007) · Acta Neuropathologica · doi:10.1007/s00401-006-0185-2 · Cited by 166
Glucocerebrosidase is shaking up the synucleinopathies
Siebert, M., Sidransky, E., & Westbroek, W. (2014) · Brain · doi:10.1093/brain/awu002 · Cited by 147
Neonatal porencephaly and adult stroke related to mutations in collagen IV A1
van der Knaap, M. S., Smit, L. M. E., Barkhof, F., Pijnenburg, Y. A. L., Zweegman, S., Niessen, H. W. M., Imhof, S. M., & Heutink, P. (2005) · Annals of Neurology · doi:10.1002/ana.20715 · Cited by 147
Self-citationDefective Glial Maturation in Vanishing White Matter Disease
Bugiani, M., Boor, I., van Kollenburg, B., Postma, N. L., Polder, E., van Berkel, C. G. M., van Kesteren, R. E., Windrem, M. S., Hol, E. M., Scheper, G. C., et al. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318203ae74 · Cited by 139
Self-citationCOL4A2 mutation associated with familial porencephaly and small-vessel disease
Verbeek, E., Meuwissen, M. E. C., Verheijen, F. W., Govaert, P. P., Licht, D. J., Kuo, D. S., Poulton, C. J., Schot, R., Lequin, M. H., Dudink, J., et al. (2012) · European Journal of Human Genetics · doi:10.1038/ejhg.2012.20 · Cited by 119
Seyrantepe, V., Hinek, A., Peng, J., Fedjaev, M., Ernest, S., Kadota, Y., Canuel, M., Itoh, K., Morales, C. R., Lavoie, J., et al. (2008) · Circulation · doi:10.1161/circulationaha.107.733212 · Cited by 112
Co-aggregate formation of CADASIL-mutant NOTCH3: a single-particle analysis
Duering, M., Karpinska, A., Rosner, S., Hopfner, F., Zechmeister, M., Peters, N., Kremmer, E., Haffner, C., Giese, A., Dichgans, M., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr237 · Cited by 109
Rudenko, G., Bonten, E., d'Azzo, A., & GJ Hol, W. (1995) · Structure · doi:10.1016/s0969-2126(01)00260-x · Cited by 97
Exome sequencing reveals mutated SLC19A3 in patients with an early-infantile, lethal encephalopathy
Kevelam, S. H., Bugiani, M., Salomons, G. S., Feigenbaum, A., Blasér, S., Prasad, C., Häberle, J., Barić, I., Bakker, I. M. C., Postma, N. L., et al. (2013) · Brain · doi:10.1093/brain/awt054 · Cited by 97
Self-citationLow, W.-C., Junna, M., Börjesson‐Hanson, A., Morris, C. M., Moss, T., Stevens, D., Clair, D. S., Mizuno, T., Zhang, W. W., Mykkänen, K., et al. (2007) · Brain · doi:10.1093/brain/awl360 · Cited by 74
Cardiopulmonary effects of endothelin-1 in man
Kiely, D. G. (1997) · Cardiovascular Research · doi:10.1016/s0008-6363(96)00219-2 · Cited by 65
Protective Protein as an Endogenous Endothelin Degradation Enzyme in Human Tissues
Itoh, K., Kase, R., Shimmoto, M., Satake, A., Sakuraba, H., & Suzuki, Y. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.2.515 · Cited by 65
Neuropathology and Genetics of Cerebroretinal Vasculopathies
Kolar, G. R., Kothari, P. H., Khanlou, N., Jen, J. C., Schmidt, R. E., & Vinters, H. V. (2014) · Brain Pathology · doi:10.1111/bpa.12178 · Cited by 58
MRI Features of Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy (PADMAL)
Ding, X. Q., Hagel, C., Ringelstein, E. B., Buchheit, S., Zeumer, H., Kuhlenbäumer, G., Appenzeller, S., & Fiehler, J. (2010) · Journal of Neuroimaging · doi:10.1111/j.1552-6569.2008.00336.x · Cited by 50
A novel hereditary small vessel disease of the brain
Verreault, S., Joutel, A., Riant, F., Neves, G., Silva, M. R., Maciazek, J., Tournier‐Lasserve, E., Bousser, M., & Chabriat, H. (2006) · Annals of Neurology · doi:10.1002/ana.20775 · Cited by 38
A novel hereditary extensive vascular leukoencephalopathy mapping to chromosome 20q13
Hervé, D., Chabriat, H., Rigal, M., Dalloz, M., Marchini, A. K., Lepeleire, J. D., Fontaine, B., Groote, C. C., Alili, N., Miné, M., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e3182768954 · Cited by 32
Adult-onset painful axonal polyneuropathy caused by a dominantNAGLUmutation
Tétreault, M., Gonzalez, M., Dicaire, M., Allard, P., Gehring, K., LeBlanc, D., Leclerc, N., Schondorf, R., Mathieu, J., Zuchner, S. L., et al. (2015) · Brain · doi:10.1093/brain/awv074 · Cited by 31
Serine Carboxypeptidases in Regulation of Vasoconstriction and Elastogenesis
Pshezhetsky, A. V., & Hinek, A. (2009) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2009.03.002 · Cited by 30
Proteolytic Activation of Human Cathepsin A
Kolli, N., & Garman, S. C. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.524280 · Cited by 30
Zhang, W. W., Badonic, T., Höög, A., Jiang, M. H., Ma, K. C., Nie, J. X., Olsson, Y., & Sourander, P. (1994) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000106714 · Cited by 30
Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies
Révész, T., Holton, J. L., Lashley, T., Plant, G. T., Frangione, B., Rostagno, A. A., & Ghiso, J. A. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0555-7 · Cited by 28
Nordborg, C., Kyllerman, M., CONRADI, N. G., & Månsson, J. (1997) · Acta Neuropathologica · doi:10.1007/s004010050579 · Cited by 25
Strisciuglio, P., Parenti, G., Giudice, C., Lijoi, S., Hoogeveen, A. T., & d’Azzo, A. (1988) · Human Genetics · doi:10.1007/bf01790104 · Cited by 19
Exome sequencing reveals mutated SLC19A3 in patients withan early-infantile, lethal, encephalopathy
Kevelam, S. H. G., Bugiani, M., Salomons, G. S., Feigenbaum, A., Blaser, S., Prasad, C., Häberle, J., Barić, I., Bakker, I. M. C., Postma, N. L., et al. (2013) · Tijdschrift voor Kindergeneeskunde · doi:10.1007/s12456-013-0062-6
Self-citation
Cited by
Sorted by citations
Small vessel disease: mechanisms and clinical implications
Wardlaw, J. M., Smith, C., & Dichgans, M. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30079-1 · Cited by 1,777
Epidemiology, aetiology, and management of ischaemic stroke in young adults
Ekker, M. S., Boot, E. M., Singhal, A. B., Tan, K. S., Debette, S., Tuladhar, A. M., & de Leeuw, F. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30233-3 · Cited by 506
van der Knaap, M. S., & Bugiani, M. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1739-1 · Cited by 403
Self-citationMancuso, M., Arnold, M., Bersano, A., Burlina, A. P., Chabriat, H., Debette, S., Enzinger, C., Federico, A., Filla, A., Finsterer, J., et al. (2020) · European Journal of Neurology · doi:10.1111/ene.14183 · Cited by 205
Stroke genetics: discovery, biology, and clinical applications
Dichgans, M., Pulit, S. L., & Rosand, J. M. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30043-2 · Cited by 187
Metadata
- Authors
- Bugiani, M., Kevelam, S. H., Bakels, H. S., Waisfisz, Q., Ceuterick-de Groote, C., Niessen, H. W. M., Abbink, T. E. M., Lesnik Oberstein, S. A. M. J., & van der Knaap, M. S.
- Affiliations
- University of Antwerp (BE)
- From the Departments of Child Neurology (M.B., S.H.K., H.S.B., T.E.M.A., M.S.v.d.K.) and Pathology (M.B., H.W.M.N.), Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam; Department of Clinical Genetics (Q.W.), VU University Medical Center, Amsterdam, the Netherlands; Laboratory for Ultrastructural Neuropathology (C.C.-d.G.), Institute Born-Bunge and University of Antwerp, Belgium; Department of Clinical genetics (S.A.M.J.L.O.), Leiden University Medical Center, Leiden; and...
- Venue
- Neurology
- Published
- 2016-10-25
- Volume
- 87
- Issue
- 17
- Pages
- 1777-1786
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2522033536
- Semantic Scholar
- 17c5f532a5c7b96787e75531436bfac66b5f5ab9
- Cited by
- 111
- References
- 40
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 16 · 2023: 10 · 2022: 16 · 2021: 9 · 2020: 13 · 2019: 13 · 2018: 13 · 2017: 9 · 2016: 1
- FWCI
- 9.02
- Type
- journal article
- Language
- en
- Update notices
- correction (2017-01-16)
- Open access
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Cerebrovascular and genetic disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
- Keywords
- cathepsin A, Clinical and Translational Science Awards, leukoencephalopathy, cerebral small vessel disease, ischemic stroke, hemorrhagic stroke, endothelin-1, oligodendrocyte progenitors, white matter astrocytes, familial stroke, treatment-resistant hypertension, cognitive decline, haplotype analysis
- MeSH terms
- Adult, Aged, Brain, Family Health, Female, Hemorrhage, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Neurologic Examination, Endothelins, Microsatellite Repeats, Stroke, Cathepsin A, Vascular Malformations, Genome-Wide Association Study, 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.
A language model drew the claims from the paper on 2026-11-02, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-02 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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 ›
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