Development, validation and implementation of neurodegenerative diseases biomarkers in cerebrospinal fluid and plasma into treatment trials and clinical studies (eg, ADNI study; UPENN ADRC; PPMI study). These studies include the use of manual and highly automated immunoassays and for amyloid beta(1-42), U-p53AZ and for total tau the use of high sensitivity UPLC/tandem mass spectrometry. Multi-modal statistical analyses of these study data to address several questions including the diagnostic utilities of these biomarkers; assessments of the longitudinal trajectories of these biomarkers in AD, MCI and cognitively normal controls to assess the neuropathological changes over time in these individuals.