Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), if specific, sensitive, and quantitative, would allow diagnosis in individuals prior the development of extensive neuronal damage. Unfortunately, current biomarkers which evaluate some of the histopathologically recognized components of AD, plaques Ab1-42) or tangles (tau or phosphorylated tau) do not fulfill the need for clinically useful tools. Work from our laboratory has identified an elevated level of a novel CSF biomarker in subjects with AD which may serve this purpose. We will determine the level of this biomarker in individuals with Mild Cognitive Impairment (MCI) compared to age-matched cognitively normal controls. CSF in these individuals will then be assayed for the novel biomarker, Ab1-42 and phosphorylated tau. This project will test the hypothesis that this new CSF biomarker will be able to identify individuals with MCI at risk for AD. Early detection of AD will then be both necessary and essential to identify interventions that slow or prevent the onset of dementia. ? ? ?