CADASIL Evidence Ledger
Every CADASIL claim this site makes, in one table: what we say, where it comes from, how strong the evidence is, and when we last checked. Built from the same files that render the pages, so it cannot drift from them. If a row is wrong, the page is wrong, and we want to know.
9 page summaries · 23 questions · 10 research entries · version · Download JSON · CC BY 4.0, cite as “The Goodyear Foundation, CADASIL Evidence Ledger”.
| Claim | Page | Sources | Evidence | Last checked |
|---|---|---|---|---|
| CADASIL is the most common inherited cause of stroke and vascular dementia in adults. It's caused by a mutation in the NOTCH3 gene that damages the brain's small blood vessels, leading to migraines, repeated strokes, and gradual cognitive decline. There is no cure yet, but the disease course varies widely and can be influenced. | CADASIL | NIH GeneReviews | Established | |
| CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is an inherited disease of the brain's small blood vessels, caused by a mutation in the NOTCH3 gene. Each child of an affected parent has a 50% chance of inheriting it. | What is CADASIL? | NIH GeneReviews (NBK1500); NINDS CADASIL page; Front Neurol 2025 NOTCH3-spectrum review | Established | |
| Is CADASIL hereditary? Yes — autosomal dominant; each child of an affected parent has a 50% chance of inheriting the gene. | What is CADASIL? | NIH GeneReviews (NBK1500); NINDS CADASIL page; Front Neurol 2025 NOTCH3-spectrum review | Established | |
| What gene causes CADASIL? NOTCH3, on chromosome 19. | What is CADASIL? | NIH GeneReviews (NBK1500); NINDS CADASIL page; Front Neurol 2025 NOTCH3-spectrum review | Established | |
| Is CADASIL contagious? No. It is genetic, not infectious. | What is CADASIL? | NIH GeneReviews (NBK1500); NINDS CADASIL page; Front Neurol 2025 NOTCH3-spectrum review | Established | |
| Can you have CADASIL without a family history? Rarely — new (“de novo”) mutations occur but are uncommon. | What is CADASIL? | NIH GeneReviews (NBK1500); NINDS CADASIL page; Front Neurol 2025 NOTCH3-spectrum review | Established | |
| CADASIL symptoms usually appear in this order: migraine with aura (often starting in the 20s–30s), recurrent strokes and TIAs (40s–50s), mood changes and apathy throughout, and progressive cognitive decline that can reach dementia by around 65. Onset and severity vary widely, even within the same family. | Symptoms & progression | NIH GeneReviews; AHA Scientific Statement; patient-reported-outcomes survey (PMC12955081) | Established (fatigue prominence: Emerging) | |
| What is usually the first sign of CADASIL? Often migraine with aura, sometimes years before strokes. | Symptoms & progression | NIH GeneReviews; AHA Scientific Statement; patient-reported-outcomes survey (PMC12955081) | Established (fatigue prominence: Emerging) | |
| Does CADASIL cause dementia? It can — progressive vascular cognitive impairment is common in later stages. | Symptoms & progression | NIH GeneReviews; AHA Scientific Statement; patient-reported-outcomes survey (PMC12955081) | Established (fatigue prominence: Emerging) | |
| Is depression part of CADASIL? Yes — mood changes and apathy are core features, and treatable. | Symptoms & progression | NIH GeneReviews; AHA Scientific Statement; patient-reported-outcomes survey (PMC12955081) | Established (fatigue prominence: Emerging) | |
| CADASIL is diagnosed with an MRI showing characteristic white-matter changes (especially in the anterior temporal poles) plus genetic testing for a NOTCH3 mutation, which is the definitive test. A skin biopsy is sometimes used when genetic testing is inconclusive. | How CADASIL is diagnosed | NIH GeneReviews; MedLink; Medscape workup | Established | |
| What does CADASIL look like on an MRI? Symmetric white-matter changes, classically in the anterior temporal poles, plus small deep strokes and microbleeds. | How CADASIL is diagnosed | NIH GeneReviews; MedLink; Medscape workup | Established | |
| Is there a genetic test for CADASIL? Yes — a NOTCH3 test is the definitive diagnosis. | How CADASIL is diagnosed | NIH GeneReviews; MedLink; Medscape workup | Established | |
| Do I need a skin biopsy? Usually only if genetic testing is inconclusive. | How CADASIL is diagnosed | NIH GeneReviews; MedLink; Medscape workup | Established | |
| There is no cure for CADASIL and no treatment proven to stop it. Care focuses on preventing strokes — controlling blood pressure, not smoking, managing vascular risk factors — plus treating migraines and depression. Some common stroke drugs (strong blood thinners and clot-busters) carry extra bleeding risk in CADASIL and are used with caution. | Treatment & management | NIH GeneReviews; NINDS; AHA/Stroke (incl. 2024 IVT case series) | Established (tPA: evolving) | |
| Is there a cure for CADASIL? Not yet. Management focuses on stroke prevention and symptom control. | Treatment & management | NIH GeneReviews; NINDS; AHA/Stroke (incl. 2024 IVT case series) | Established (tPA: evolving) | |
| What's the most important thing I can do? Control blood pressure and don't smoke — the highest-yield, best-evidenced levers. | Treatment & management | NIH GeneReviews; NINDS; AHA/Stroke (incl. 2024 IVT case series) | Established (tPA: evolving) | |
| Can CADASIL patients take aspirin? Sometimes considered for prevention; discuss with your neurologist. Strong blood thinners are used more cautiously. | Treatment & management | NIH GeneReviews; NINDS; AHA/Stroke (incl. 2024 IVT case series) | Established (tPA: evolving) | |
| Is tPA safe in CADASIL? Guidelines are cautious due to bleeding risk; it's decided case-by-case. Tell any ER you have CADASIL. | Treatment & management | NIH GeneReviews; NINDS; AHA/Stroke (incl. 2024 IVT case series) | Established (tPA: evolving) | |
| In CADASIL, strokes happen because the NOTCH3 mutation damages the brain's small blood vessels, not because of clots from the heart or large arteries. They are the most common presenting sign, typically in mid-life. Prevention centers on controlling blood pressure and vascular risk factors; some standard stroke drugs need caution here. | Stroke & CADASIL | NIH GeneReviews; NINDS; AHA Scientific Statement | Established | |
| Why do strokes happen in CADASIL? The NOTCH3 mutation damages the brain's small blood vessels, causing small deep (lacunar) strokes — not clots from the heart or large arteries. | Stroke & CADASIL | NIH GeneReviews; NINDS; AHA Scientific Statement | Established | |
| How are CADASIL strokes prevented? By controlling blood pressure and vascular risk factors and not smoking; strong blood thinners are used with caution. See the Treatment page. | Stroke & CADASIL | NIH GeneReviews; NINDS; AHA Scientific Statement | Established | |
| There is no proven cure for CADASIL. Be cautious of online claims — including methylene blue. No study has shown methylene blue helps CADASIL in humans or animals; a widely-shared claim of “Harvard/Yale methylene blue CADASIL mouse research” does not exist and appears to be an AI-fabricated citation. Real hope is in early-stage gene-targeted research. | “Is there a cure?” | clinicaltrials.gov (null result for MB+CADASIL); ALZFORUM (LMTX Phase 3 failure); FDA label (serotonin-syndrome); CADASIL therapy reviews | The absence of methylene-blue evidence is Established. | |
| Does methylene blue help CADASIL? There is no evidence it does, and real safety risks — do not self-dose, especially on antidepressants. | “Is there a cure?” | clinicaltrials.gov (null result for MB+CADASIL); ALZFORUM (LMTX Phase 3 failure); FDA label (serotonin-syndrome); CADASIL therapy reviews | The absence of methylene-blue evidence is Established. | |
| Was there a Harvard/Yale study on methylene blue and CADASIL? No. That claim does not correspond to any real study and appears to be an AI-fabricated citation. | “Is there a cure?” | clinicaltrials.gov (null result for MB+CADASIL); ALZFORUM (LMTX Phase 3 failure); FDA label (serotonin-syndrome); CADASIL therapy reviews | The absence of methylene-blue evidence is Established. | |
| Is there any promising CADASIL research? Yes — gene-targeted approaches (exon-skipping, base editing, immunotherapy) are in early development. | “Is there a cure?” | clinicaltrials.gov (null result for MB+CADASIL); ALZFORUM (LMTX Phase 3 failure); FDA label (serotonin-syndrome); CADASIL therapy reviews | The absence of methylene-blue evidence is Established. | |
| Living with CADASIL means managing what you can — blood pressure, activity, mental health — while getting support for what you can't. The disease course varies widely; many people stay stable for years. Depression, apathy, and fatigue are common and treatable, and caregiver support matters as much as patient care. | Living with CADASIL | Opherk 2004 (Brain); 18-year cohort (PMC7900403); American Brain Foundation | Established | |
| What is the life expectancy with CADASIL? It varies widely; peer-reviewed medians are ~65 (men)/~71 (women), but many people remain stable for years. Baseline health matters most. | Living with CADASIL | Opherk 2004 (Brain); 18-year cohort (PMC7900403); American Brain Foundation | Established | |
| Does everyone with CADASIL end up with dementia? No — severity varies greatly; some remain mild for a long time. | Living with CADASIL | Opherk 2004 (Brain); 18-year cohort (PMC7900403); American Brain Foundation | Established | |
| Where do I find a CADASIL-literate doctor? Seek neurologists or academic centers experienced in small-vessel disease; advocacy groups like cureCADASIL can help. | Living with CADASIL | Opherk 2004 (Brain); 18-year cohort (PMC7900403); American Brain Foundation | Established | |
| CADASIL research is active: gene-targeted therapies (exon-skipping, base editing, immunotherapy) are in preclinical development, and trials of cilostazol and stem-cell therapies are underway. This page tracks new findings and grades them honestly — promising, early, or unproven. | Living research guide | PubMed; clinicaltrials.gov | Emerging | |
| Is there promising CADASIL research? Yes — gene-targeted approaches (exon-skipping, base editing, immunotherapy) are in preclinical development, with cilostazol and stem-cell trials underway. None is FDA-approved yet. | Living research guide | PubMed; clinicaltrials.gov | Emerging | |
| The outlook for CADASIL appears to be improving. A 23-year UK study of 555 people with genetically confirmed CADASIL found that the age at first stroke rose over time, that people recruited after 2016 had a lower risk of both stroke and dementia, and that people who stopped smoking at any point were significantly more likely to remain stroke- and dementia-free. The authors say these updated figures should be used when counselling patients. | Living research guide | Sukhonpanich et al., J Neurol Neurosurg Psychiatry (2025) | Human study | |
| US CADASIL Consortium: baseline findings presented. The NIH-funded US CADASIL Consortium (University of Wisconsin–Madison lead, 12 US sites) is a 575-person observational study of how CADASIL begins and progresses. Baseline findings were presented at the International Stroke Conference (February 2026) and the Alzheimer's Association International Conference (July 2026), including executive dysfunction as the cardinal cognitive feature. It is still recruiting adults 18+ with a NOTCH3 result or willing to be tested, plus family members without the gene as a comparison group. | Living research guide | ClinicalTrials.gov NCT05677880; cadasil.wisc.edu | Trial | |
| CERICA: a placebo-controlled trial of Cerebrolysin in CADASIL. A randomized, double-blind, placebo-controlled crossover trial (single centre, Czechia) is testing whether Cerebrolysin, an intravenous peptide preparation, is safe and helps people with genetically proven CADASIL. It is active but no longer enrolling. No results have been published yet. | Living research guide | ClinicalTrials.gov NCT05755997 | Trial | |
| Selective NOTCH3 inhibitors block mutant-receptor clumping in the lab. Researchers showed that CADASIL-mutant NOTCH3 receptors only clump together when normal NOTCH3 is also present, and that peptide inhibitors built to target NOTCH3 specifically can block both the clumping and the abnormal signalling in cell-based assays. This is cell work, not an animal or human study. | Living research guide | Wang et al., FASEB J (2026) | Preclinical | |
| First zebrafish model of CADASIL. A Chiba University team created zebrafish carrying a human-equivalent NOTCH3 mutation (p.C680S) that reproduce several age-dependent vascular and neurological features of CADASIL, and implicate type IV collagen in disease progression. A new model, not a treatment; its value is faster drug screening in the years ahead. | Living research guide | Kanoh et al., Acta Neuropathol Commun (2026) | Preclinical | |
| Review: NOTCH3 damage may reach beyond blood vessels. A 2026 review gathers evidence that NOTCH3 mutations also affect astrocytes (the brain's waste-clearing glymphatic system), oligodendrocytes (myelin) and the blood-brain barrier, not only the smooth-muscle cells around small arteries. It proposes patient-derived 'organoid' models and astrocyte-targeted therapies as research directions. A review of mechanisms, not a treatment. | Living research guide | Lee et al., Cell Commun Signal (2026) | Preclinical | |
| NOTCH3 mutations alter lipid metabolism in patient plasma and cells. Lipid profiling found measurable differences in the blood of people with CADASIL compared with healthy controls, and cell models carrying several common mutations showed raised cholesterol and lipid-droplet build-up. Early biomarker work; it does not change treatment today. | Living research guide | Neurochem Res (2026) | Preclinical | |
| 'CADASIL in a dish': patient stem-cell blood-vessel models (Cambridge). The University of Cambridge CADASIL clinic (Prof. Hugh Markus; Dr Alessandra Granata) is turning patients' own stem cells into brain-blood-vessel cells to study why vessels fail and to test protective drugs. Updates were given at the Cambridge CADASIL Meeting on 3 March 2026, alongside work on blood biomarkers and modifier genes. Funded in part by CADASIL Support UK. | Living research guide | Cambridge CADASIL Meeting 2026 | Preclinical | |
| cureCADASIL Patient-Investigator Meeting (June 27, 2026). cureCADASIL's half-day meeting for patients, families and researchers ran alongside the United Leukodystrophy Foundation conference in Oak Brook, Illinois, supported by a Chan Zuckerberg Initiative grant. Its webinar archive (CADASIL Connection series) is free and includes the CZI-funded patient-partnered drug-target work led by Dr Fanny Elahi. | Living research guide | cureCADASIL | Established | |
| An international severity staging system for NOTCH3 small-vessel disease. An international cohort study developed and validated a staging system for NOTCH3-associated small-vessel disease (including CADASIL), tying stages to MRI findings, cognition and blood NfL levels. Useful for trials and for talking about 'where someone is' in the disease; it is not a treatment. | Living research guide | JAMA Neurology (2024) | Human study |
How to read the grades
- Established: in guidelines or large human cohorts.
- Human study: human data, not yet practice-changing.
- Trial: an interventional or observational study you can join or follow.
- Emerging / Preclinical: early work in cells, animals or small series.
No clinician has yet reviewed this ledger. We say so rather than invent a name; see the medical review board page.