Abstract: Provided herein are APP RNAi agents and compositions comprising an APP RNAi agent. Also provided herein are methods of using the APP RNAi agents or compositions comprising an APP RNAi agent in reducing APP expression and/or treating APP associated neurological diseases.

Abstract: Provided herein are proteins comprising one monovalent human TfR binding domain (“human TfR binding proteins”), proteins comprising one monovalent mouse TfR binding domain (“mouse TfR binding proteins”), conjugates comprising such human or mouse TfR binding proteins, e.g., human TfR binding proteins-dsRNA conjugates, pharmaceutical compositions comprising human TfR binding proteins or conjugates, and methods of treating CNS diseases (e.g., neurodegenerative disease such as neurodegenerative synucleinopathy or tauopathy) using human TfR binding proteins or conjugates.