Case study of a unique variant in the NOTCH-3 gene in 10 AD cases

 
   Lead Investigator:    Jesse Mez
   Institution      :    Boston University
   E-Mail           :    jessemez@bu.edu
   Proposal ID      :    904



   Proposal Description:
   As part of the Alzheimer???s Disease Sequencing Project (ADSP), we identified a   a unique variant in the NOTCH-3 gene in 10 AD cases, but no controls among        approximately 5000 AD cases and 5000 controls. NOTCH-3 mutations have been        identified as the etiology of CADASIL (Cerebral Autosomal-Dominant Arteriopathy   with Subcortical Infarcts and Leukoencephalopathy), but variants in NOTCH-3       have not previously been associated with AD.  Five of the 10 AD cases were from   the ADCs.  We are interested in clinically characterizing these individuals.      We are requesting a wide array of data on these individuals, including vascular   risk factors, history of or exam findings consistent with stroke,                 neuropsychological profile, evidence of AD biomarkers, MRI images, dementia       course, neuropathology and family history.  Rare TREM-2 variants have been implicated in Alzheimer's Disease. The clinical presentation of those with these variants is not well understood. As part of the analyses we conducted for this project we also identified rare variants in TREM-2 that were only in cases and not controls. We seek to understand the clinical presentation of these individuals with these rare variants.