Abstract
Based on genetic findings, the relationship between the APP/Aβ and tau/tangle pathologies are discussed. It is argued that APP/Aβ is upstream of tau/tangle in the Alzheimer pathogenesis, and that the relationship between the pathologies are promiscuous in two ways: first, APP/Aβ can equally be seen to be upstream of synuclein/Lewy bodies in cell death pathways, and second, tau pathology can be initiated by genetic lesions in other pathways.