New Clinical Approaches to Creutzfeldt-Jakob Disease

克雅氏病（Creutzfeldt-Jakob disease， CJD）是一种快速进展的、普遍致命的、可传播的神经退行性疾病，给患者及其家庭带来了可怕的负担。最近发现，阿奎宁可能是一种潜在的治疗克雅氏病的方法，这可能对患者产生巨大的影响。不幸的是，患者通常是在疾病的晚期被诊断出来的，这时可用的治疗可能无效。这种延迟诊断的部分原因是目前散发性CJD （sCJD）的临床标准是基于通常只在患者病程后期出现的一系列症状。

DESCRIPTION (provided by applicant): Creutzfeldt-Jakob disease (CJD)is a rapidly progressive, universally fatal, and transmissible neurodegenerative disease that imposes a terrible burden on patients and their families. The recent discovery that quinacrine may be a potential therapy for CJD could have enormous implications for patients. Unfortunately, patients are usually diagnosed in advanced stages of the disease - a time when available treatments may be ineffective. This delayed diagnosis is in part because current clinical criteria for sporadic CJD (sCJD) are based on a constellation of symptoms that often occur only late in a patient's course. Recently, neuroimaging has shown potential to improve the diagnosis of sCJD. Additionally, an elevated level of the protein 14-3-3 in the cerebrospinal fluid (CSF) has been touted as a sensitive and specific biomarker for sCJD and has recently been added to the diagnostic criteria for sCJD. Yet, no systematic study has been undertaken to identify the sensitivity and specificity of these two types of biomarkers in pathologically proven sCJD versus non-prion rapidly progressive dementias. The research goals of this proposal focus on identifying better ways for early diagnosis of CJD through a systematic analysis of clinical and imaging findings. The specific aims of this research will be as follows: 1 . To determine the sensitivity and specificity of diffusion-weighted imaging (DWI) sequence abnormalities in sporadic CJD, and 2. To determine the sensitivity and specificity of the CSF 14-3-3 protein as a marker for sporadic CJD. This research should provide new information on the early features of sCJD and thus facilitate diagnosis. In addition, this proposal will combine didactic teaching, mentoring, and clinical research experience to build upon Dr. Geschwind's training in behavioral neurology and neuroscience, thereby helping him to design and implement future clinical treatment studies for human prion disease and other dementias.