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Published on: March 7, 2019
Hereditary cerebral amyloid angiopathy mimicking CADASIL syndrome
Klearchos Psychogios1,2, Georgia Xiromerisiou3, Odysseas Kargiotis1
1Stroke Unit, Metropolitan Hospital, Piraeus, Greece.
Insights
A rare form of cerebral amyloid angiopathy (hCAA) in a Greek family mimicked CADASIL, a small vessel disease. This case highlights a novel mutation causing CADASIL-like symptoms and brain imaging findings.
Area of Science:
- Neurology
- Genetics
- Vascular Neurology
Background:
- Small vessel diseases (SVDs) like CADASIL and hereditary cerebral amyloid angiopathy (hCAA) are clinically significant.
- This study reports a rare Greek family with hCAA exhibiting a CADASIL-like phenotype.
Observation:
- A 65-year-old man presented with transient leg numbness, cognitive decline, and a family history of stroke, dementia, and migraine.
- Brain imaging revealed CADASIL-like leukoencephalopathy, occipital calcifications, and microbleeds.
- Genetic testing excluded NOTCH3 mutations but identified a novel hCAA pathogenic mutation.
Findings:
- A novel amyloid precursor protein mutation was identified in a Greek family.
- The mutation resulted in a clinical phenotype resembling CADASIL, including cognitive and motor decline, stroke, migraine, and behavioral issues.
- Neuroimaging showed leukoencephalopathy, occipital calcifications, and microbleeds consistent with CADASIL.
Implications:
- This case underscores the importance of considering hCAA in patients presenting with CADASIL-like symptoms.
- Early diagnosis of hCAA can facilitate timely preventive strategies and potential disease-modifying treatments.
- Identifying novel mutations expands our understanding of the genetic basis of small vessel diseases.
Background:
Small vessel disease (SVD), and most specifically hereditary forms like CADASIL and cerebral amyloid angiopathy (hCAA), are conditions of increasing clinical importance. We report a rare case of hCAA in a Greek family that presented with a CADASIL clinical and neuroimaging phenotype.
Methods:
A 65-year-old man was admitted with recurrent transient episodes of right leg numbness. The patient's medical history started at the age of 50 years with depression and behavioral disorders. His family history was positive for stroke (father), dementia (father and brother), migraine (daughter) and depression (father and daughter).
Results:
Neurological examination disclosed anomic aphasia with severely impaired cognitive status, and brisk reflexes. Brain computed tomography and magnetic resonance imaging showed CADASIL-like leukoencephalopathy (hyperintense lesions in bilateral temporopolar area, external capsule, thalami, centrum semiovale and superior frontal regions) with occipital calcifications and cerebral microbleeds. Screen for variants in NOTCH3 gene was negative. Exome sequencing revealed a novel pathogenic mutation for hCAA.
Conclusions:
We report a novel amyloid precursor protein mutation which results in a CADASIL-like clinical phenotype (progressive cognitive and motor decline, stroke, migraine and behavioral disorders) and CADASIL-leukoencephalopathy coupled with occipital calcifications. Earlier recognition and swift hCAA diagnosis may prompt rational preventive and potential disease-modifying interventions.
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