<h4>Introduction</h4>Alpha-synuclein (αSyn) is the most common co-pathology in Alzheimer's disease (AD), yet its role within the amyloid-tau-neurodegeneration (ATN) cascade is unknown.<h4>Methods</h4>We analyzed 636 ADNI participants with CSF αSyn seed amplification assay, amyloid PET, regional tau PET (Braak I-VI), structural MRI, and cognitive composites. Here, MAPT is linked to Alzheimer disease.