Related Experiment Video
Updated: May 2, 2026
04:29
Author Spotlight: Modeling Vascular Contributions to Alzheimer's Disease in Transgenic Mice
Published on: May 17, 2024
1.3K
Early-onset stroke and vasculopathy associated with mutations in ADA2
Qing Zhou1, Dan Yang, Amanda K Ombrello
1The authors' affiliations are listed in the Appendix.
The New England Journal of Medicine
|February 21, 2014
Summary
Recessive mutations in CECR1, encoding adenosine deaminase 2 (ADA2), cause a spectrum of vascular and inflammatory disorders. Loss of ADA2 function leads to phenotypes from childhood stroke to systemic vasculitis.
Area of Science:
- Genetics
- Vascular Biology
- Immunology
Background:
- Observed a syndrome of intermittent fevers, early-onset lacunar strokes, livedoid rash, hepatosplenomegaly, and systemic vasculopathy.
- Suspected a genetic cause due to early childhood onset.
Purpose of the Study:
- Investigate the genetic basis of a rare syndrome presenting with neurovascular and inflammatory manifestations.
- Identify the gene responsible for a spectrum of vasculopathic and inflammatory disorders.
Main Methods:
- Performed whole-exome and candidate-gene sequencing on nine affected patients.
- Conducted enzyme assays, immunoblotting, immunohistochemistry, flow cytometry, and cytokine profiling.
- Utilized zebrafish and cell culture models to assess protein function.
Main Results:
- Identified recessively inherited, deleterious mutations in CECR1 (encoding ADA2) in all nine patients.
- Demonstrated reduced ADA2 levels and enzyme activity in patients.
- Observed vasculopathic changes and inflammation in patient tissues; zebrafish models recapitulated key phenotypes.
Conclusions:
- Loss-of-function mutations in CECR1 are associated with a range of vascular and inflammatory phenotypes.
- These phenotypes include early-onset stroke, systemic vasculopathy, and vasculitis.
- The study implicates ADA2 deficiency in diverse clinical presentations.
More Related Videos
09:45Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke
Published on: March 22, 2016
9.8K
05:12A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
Published on: November 22, 2024
1.7K
Related Concept Videos
01:22Dementia l: Introduction
35
Dementia is an acquired, progressive syndrome characterized by a decline in multiple cognitive domains severe enough to impair daily functioning and reduce independence. Although memory loss is a central feature, the diagnosis requires additional deficits involving language, executive function, visuospatial skills, judgment, calculation, or abstract reasoning. These cognitive impairments reflect underlying neurodegenerative or vascular processes that gradually disrupt neuronal networks...
35
01:29Alzheimer Disease l: Introduction
21
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
21
01:15Ischemic Stroke ll: Pathophysiology
54
An ischemic stroke occurs when a cerebral blood vessel becomes obstructed, most often by a thrombus or embolus, interrupting the delivery of oxygen and glucose to brain tissue. Because neurons rely on continuous aerobic metabolism, energy failure begins within minutes of reduced perfusion. The region receiving the least blood flow becomes the infarct core, an area of irreversible cellular death. Surrounding this core lies the penumbra, a zone of hypoperfused but still viable tissue that is...
54
01:23Alzheimer Disease ll: Pathophysiology
35
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and...
35
01:30Peripheral Artery Disease I: Introduction
659
Peripheral artery disease (PAD) predominantly results from atherosclerosis, which involves the accumulation of fatty deposits, or plaques, within the walls of arteries. This causes them to narrow and harden, significantly reducing blood flow. PAD predominantly affects the legs, particularly the arteries supplying the thighs and calves. In rare cases, it may involve other arteries, including those in the arms.Etiology of PAD:The principal cause of PAD is atherosclerosis, which results from fatty...
659
01:29Hemorrhagic Stroke ll: Pathophysiology
30
A hemorrhagic stroke develops when a cerebral blood vessel ruptures, allowing blood to escape into the surrounding brain tissue, as in intracerebral hemorrhage (ICH), or into the subarachnoid space, as in subarachnoid hemorrhage (SAH). Because the skull is a rigid compartment, the sudden presence of extravascular blood rapidly increases intracranial pressure and compresses adjacent neural structures, leading to immediate tissue injury and impaired cerebral perfusion.Mass Effect and Primary...
30