This is the first large-scale, multicenter, systematic effort to

This is the first large-scale, multicenter, systematic effort to use standardized instruments to identify and uniformly evaluate individuals with the site dominantly inherited AD. The DIAN aims to determine the chronological changes in cognition and biomarkers in relation to clinical onset and progression of dementia in a well-characterized and uniformly studied group of persons at risk for ADAD. The DIAN investigators will assess and quantify the ability of clinical, biological and imaging markers to predict and track the progression of AD. The DIAN’s overriding purpose is to contribute to the search for meaningful therapies for AD by helping elucidate the cascade of events that lead to dementia of the Alzheimer’s type. The specific aims for the DIAN include the following.

First, to establish an international registry of individuals (mutation carriers and noncarriers; presymptomatic and symptomatic) who are biological adult children of a parent with a known causative mutation for AD in the APP, PSEN1, or PSEN2 genes in which the individuals are evaluated in a uniform manner at entry and longitudinally thereafter. The second aim is to obtain clinical and cognitive batteries that comprise the Uniform Data Set of the National Institutes of Health-funded Alzheimer’s Disease Centers, supplemented by web-based neuropsychological tests. A further aim is to implement structural, functional, and amyloid imaging protocols (3T MRI, fluorodeoxyglucose-PET, PiB-PET).

The fourth aim is to collect biological fluids, including blood and CSF, for DNA analysis and assays of putative biomarkers of AD, including A??42 and tau – this will also provide a resource for exploratory studies of novel biochemical markers. Finally, the DIAN aims to perform uniform AV-951 histopathological examination of cerebral tissue in individuals who come to autopsy. The National Institute on Aging awarded a 6-year grant for the DIAN that funds 10 international performance sites that combine resources and research participants of the individual sites in a uniform and comprehensive manner. Currently, over 400 individuals who are members of families with a known causative mutation for AD (that is, APP, PSEN1, PSEN2) have been identified between the sites and are eligible for participation in the DIAN. Over the first 6 years, sites will recruit, enroll and evaluate these individuals to reach a sample size of 400 participants.

The DIAN cohort download catalog is predicted to comprise 80% asymptomatic individuals (with 50% of these being mutation carriers and 50% noncarriers) and 20% symptomatic individuals. Based on the participant population demographics, the DIAN is expected to enroll 50% of individuals within 3 years of parental age at disease onset, and 30% of individuals within 3 to 10 years before parental age at disease onset.

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