Amprion has previously demonstrated that its Seeded Aggregation Amplification assay (SAA) for detection of misfolded alpha-synuclein aggregates in CSF can accurately detect the presence of Parkinson's Disease and Lewy Body Dementia with greater than 90% sensitivity and 95% specificity. More recent studies comparing alpha-synuclein SAA data with longitudinal clinical diagnosis and imaging (DaT Scan) in PD and LBD patients indicates that CSF synuclein-SAA at the time of initial diagnosis is equal or superior in predicting future progression of disease (Michael J Fox Foundation PPMI samples, Manuscript in Preparation). A recently completed ADDF-funded phase 1 study in 59 AD patients compared synuclein-SAA diagnosis in CSF at the time of initial diagnosis with autopsy pathology 7 years after initial diagnosis on average. The results of this blinded study demonstrated that AD patients with no evidence of Lewy Bodies at autopsy were accurately predicted by synuclein-SAA analysis of CSF obtained at the time of initial diagnosis (35/35). In addition, AD patients with extensive neocortical Lewy Body infiltration at autopsy were also accurately predicted with CSF-based synuclein-SAA at the time of initial diagnosis (9/9). Most importantly, all AD patients testing positive for synuclein-SAA at the time of initial diagnosis showed Lewy Bodies at autopsy. Amprion has recently moved its synuclein SAA CSF assay to a licensed CLIA laboratory and is completing analytical validation of its CLIA version of the synuclein-SAA test. We proposed to expand the AD pilot study to an additional 400 AD patients by comparing archival CSF samples from these patients with clinical diagnosis and outcomes as well as with imaging and autopsy data where available. This dataset will be used as part of an FDA submission package for market authorization of synuclein-SAA in AD and LBD patients.