The objective of this project is to identify CSF molecular markers associated with the antemortem diagnosis of Alzheimer's disease which can be used as a measure for disease pathology. In contrast to brain based studies of the molecular mechanism of disease progression, this investigation with use proteomics technology to identify and characterize CSF proteins of interest. This information can be used to categorize disease pathology or can be used to develop immunoassays for diagnosis. In order to achieve these long-term objectives, the investigator plans to: identify and obtain CSF blood samples and clinical information from an appropriate sample population of patients with different forms of dementia, probable Alzheimer's disease at various stages and controls (Specific Aim 1). Analyze the samples for AD specific protein markers used in proteome analysis that includes high solution two-dimensional electrophoresis, laser densitometry, fluorescence imaging, and computer aided in each analysis (Specific Aim 2). He employs multivariate statistics to establish a correlation between relevant changes in disease diagnosis and establish qualitative and quantitative bar code for diagnosis of Alzheimer's disease. This includes the validation of other proposed CSF markers such as tau and Abeta 42 as well as the preliminary identification of other major differential diagnosis such as vascular dementia, dementia with Lewy bodies (Specific Aim 3). Use microchemical characterization of important proteins to elucidate the genetic basis of the molecular markers and other reference proteins. This information can also be used to develop immunoassays (Specific Aim 4).
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