A fragment of the scaffolding protein RanBP9 is increased in Alzheimer's disease brains and strongly potentiates amyloid-beta peptide generation.

Increasing biochemical and genetic evidence indicates that the amyloid-beta (Abeta) peptide derived from amyloid precursor protein (APP) plays a central role in Alzheimer's disease (AD) pathogenesis. We previously reported that RanBP9 promotes Abeta generation by scaffolding APP/BACE1/LRP complexes together. Interestingly, the RanBP9-Delta1/N60 (residues 1-392) deletion mutant interacted much more strongly with APP/BACE1/LRP than full-length RanBP9.