Cerebral small vessel disease (cSVD) is a broad term used to describe vascular changes affecting small blood vessels in the brain (Pantoni et al., 2010). In addition to significantly increasing the risk for strokes, cSVD is a leading cause of vascular contributions to cognitive impairment and dementia (VCID) in the aging population (Gorelick et al., 2011). With current methodologies, the detection and quantification of cSVD in living patients (in-vivo) is challenging, and cSVD frequently goes undetected.
To better characterize the clinical trajectory associated with cSVD and to validate disease-specific biomarkers, the MAPP laboratory is currently studying a cohort of patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL).
What is CADASIL?
CADASIL is a rare autosomal-dominant hereditary disease linked to mutations on the NOTCH3 gene (Joutel et al., 1996). Patients with CADASIL can suffer from early and recurrent strokes and develop vascular cognitive impairment and dementia at a relatively young age (Chabriat et al., 2009). CADASIL is associated with other clinical symptoms, including migraines with aura, gait disturbance, and apathy (Chabriat et al., 2009). Because CADASIL represents a relatively “pure” model of cSVD and VCID, this disease can provide valuable information to advance our understanding of the causes and consequences cerebrovascular pathology.
Rendon J, Zuluaga Y, Velilla L, Ochoa J, Arboleda-Velasquez JF, Budson AE, Lopera F, Quiroz YT. Event-Related Potential Correlates of Recognition Memory in Asymptomatic Individuals with CADASIL. Brain Research. March 2019; 1707: 74-78.
Schoemaker D, Quiroz TY, Torrico-Teave H, Arboleda-Velasquez JF. Clinical and research applications of magnetic resonance imaging in the study of CADASIL. Neurosci Lett. 2019. April 17;698:173-179. doi: 10.1016/j.neulet.2019.01.014
Zuluaga-Castaño Y, Montoya-Arenas DA, Velilla L, Ospina C, Arboleda-Velasquez JF, Quiroz YT, Lopera F. Cognitive performance in asymptomatic carriers of mutations R1031C and R141C in CADASIL. International Journal of Psychological Res. 2018; 11 (2): 46-55. Doi: 10.21500/20112084.3373
Primo V, Graham M, Bigger-Allen AA, Chick JM, Ospina C, Quiroz YT, Manent J, Gygi SP, Lopera F, D’Amore PA, Arboleda-Velasquez JF. Blood biomarkers in a mouse model of CADASIL. Brain Res. 2016 Aug 1; 1644:118-26. doi: 10.1016/j.brainres.2016.05.008.
- CureCADASIL (https://curecadasil.org/) – A non-profit 501(c)(3) organization dedicated to CADASIL research, patients and their families.
- NORD (National Organization for Rare Disorders) – CADASIL (https://rarediseases.org/rare-diseases/cadasil/)
- Genetic and Rare Diseases (GARD) Information Center – CADASIL (https://rarediseases.info.nih.gov/diseases/1049/cadasil)