This is a collaborative study between leading experts in the field to extend our ongoing efforts to delineate the complete genetic basis of the two AD-specific proteinopathies (Aβ and pathologic tau) by whole genome sequencing (WGS) using well-characterized and large amyloid-PET and CSF Aβ42/tau datasets with clinical outcomes of dementia followed by testing the effects of identified significant variants on downstream neurodegeneration markers, and performing extensive bioinformatics and functional studies. The primary objective of this application is to perform and analyze WGS in adequately powered large discovery samples with well-characterized Aβ and tau data along with clinical outcomes of dementia to identify putative functional variants associated with Aβ and tau pathologies.