Banked frozen brain tissue from UDS participants with autosomal dominant AD mutation Lead Investigator: Erik Johnson Institution : Emory University E-Mail : erik.c.b.johnson@emory.edu Proposal ID : 972 Proposal Description: Aim: To compare the brain protein network alterations that characterize autosomal dominant AD with those observed in sporadic AD. Hypothesis: The molecular processes leading to dementia in autosomal dominant AD are distinct from those leading to dementia in sporadic AD, and therefore the brain protein network alterations found in each disorder will be unique. Approach: Frozen frontal cortex from APP adAD, PS1 adAD, ApoE3/E3 sAD, and ApoE3/E3 control brains will be analyzed by quantitative mass spectrometry to obtain relative quantitative protein measurements across all cases. A protein network will then be constructed using systems biology tools to identify groups of proteins that are significantly altered between cognitively normal control cases and both adAD and sAD cases. Network similarity between adAD and sAD will be assessed using differential network analysis. Module-trait associations will be made using NACC neurohistopathological measures of Abeta plaque and neurofibrillary tangle burden.