the world are working to better understand the disease process in CADASIL
and to find treatments and cures. Below are summaries of some important
recent research articles. The summaries are written so that you can
understand them even if you do not have a lot of scientific knowledge.
However, there are also links to the articles themselves.
Analysis of post-mortem tissue from CADASIL patients is critical for advancing the fight against CADASIL. Thanks to many generous donors our CADASIL Tissue Bank, directed by Professors delaMonte and Stopa, has received many tissue donations from family members with CADASIL. As far as we can tell we have the largest known tissue repository in the world for the study of CADASIL. This collection includes brain tissue and tissue from many other organs, such as spinal cord, which previously have not been examined in CADASIL patients. We are using this tissue to study fundamental processes that contribute to the loss of nerve cell function. This work has recently been published. We are preparing a new publication that will shed new light on the important overlap between CADASIL and Alzheimer’s disease. The tissue in our repository is also available for use by other investigators studying CADASIL around the world.
High power vew of brain arteriole showing replacement of the smooth muscle layer with diffuse granlular material in a patient with CADASIL
Accumulation of Notch3 protein in the wall of a small arteriole stained with antibody
Dense core granules emanating from the arteriolar wall as seen on high power electron microscopy
Click here to view a journal article on molecular changes in CADASIL arteries.
CADASIL is caused by a mutation in the NOTCH3 gene on the short arm of chromosome 19. NOTCH3 codes for a protein that regulates cell fate and helps in the repair of smooth muscle cells inside the wall of small arteries in the brain. The mutation in the NOTCH3 gene in CADASIL leads to the gradual breakdown and degeneration of small arteries in the brain and the accumulation of clumps of notch3 protein. Understanding how the genetic mutation leads to the degeneration of brain arterioles is critical for developing new treatments to keep the blood vessels healthy. Working together with our colleagues in pathology research we have identified some of the key molecular changes occurring inside the blood vessels in CADASIL patients. Working together with investigators at Athena Diagnostics and neuroscience faculty at the Brigham and Women’s Hospital in Boston, we have analyzed gene samples from more than 10,000 patients tested for CADASIL, leading to the identification of 119 mutations not previously reported. This paper is currently under review. This new information should provide valuable clues for understanding the molecular changes causing CADASIL.
Click here for an abstract describing a CADASIL mutation study.