Alzheimer's disease (AD) is a genetically complex disorder for which the 
definite diagnosis is only accomplished postmortem. Mutations in 3 genes (APP, 
PSEN1, and PSEN2) are known to cause AD, but a large number of familial cases do 
not harbor mutations in these genes and several unidentified genes that contain 
disease-causing mutations are thought to exist. We performed whole exome 
sequencing in a Turkish patient clinically diagnosed with Alzheimer's disease 
from a consanguineous family with a complex history of neurological and 
immunological disorders and identified a mutation in NOTCH3 (p.R1231C), 
previously described as causing cerebral autosomal dominant arteriopathy with 
subcortical infarcts and leukoencephalopathy (CADASIL). Complete screening of 
NOTCH3 in a cohort of 95 early onset AD cases and 95 controls did not reveal any 
additional pathogenic mutations. Although the complex history of disease in this 
family precluded us to establish segregation of the mutation found with disease, 
our results show that exome sequencing is a rapid, cost-effective and 
comprehensive tool to detect genetic mutations, allowing for the identification 
of unexpected genetic causes of clinical phenotypes. As etiological based 
therapeutics become more common, this method will be key in diagnosing and 
treating disease.