Neuroimaging of Genetically-Defined Incipient CID

Creutzfeldt-Jakob Disease (CJD), the most notable of the human prion diseases, is invariably fatal. The rarity of CJD, difficulty of early diagnosis, virulent course, and variable modes of transmission, have made clinical studies exceedingly difficult. <P> We here propose a unique method of addressing the difficulties of clinical research in this area. We will use advanced MRI methodology to elucidate early, and even premorbid, cerebral abnormalities of structure and function in such patients. We plan to capitalize on a singular cluster of high incidence occurring among Libyan Jews living in Israel, caused by familial transmission of a mutated prion protein (PrP) gene. <P> Healthy carriers of the relevant mutation (E200K) will be identified (n=50), and will be studied before, as well as after, symptomatic expression. Family members lacking the mutation will serve as controls (n=50). In addition, we will recruit into the study all incident CJD cases in Israel that carry this mutation. We believe we will be able to examine these incident cases within 2 months of onset, and follow them for the duration of the disease. All subjects will have extensive neurological and neuropsychological examinations, as well as MRI, using both traditional structural imaging and newer neuroimaging methods: Diffusion- Weighted Imaging (DWI) and Chemical Shift Imaging (CSI). <P> This project will be the largest neuroimaging study ever conducted in this disease, and the first to observe a genetically homogenous sample. Further, it will provide data on the earliest stages of the disease, including healthy mutation carriers before frank onset of symptomatology. <P> The large sample sizes, availability of healthy mutation carriers, the noncarriers of similar environmental and cultural background, and rapid access to symptomatic patients, are all unprecedented features that should yield definitive data on the early stages of this devastating disease.