Arc/Arg3.1 Regulates an Endosomal Pathway Essential for Activity-Dependent β-Amyloid Generation.  Jing Wu, Ronald S. Petralia, Hideaki Kurushima, Hiral Patel, Mi-young Jung, Lenora Volk, Shoaib Chowdhury, Jason D. Shepherd, Marlin Dehoff, Yueming Li, Dietmar Kuhl, Richard L. Huganir, Donald L. Price, Robert Scannevin, Juan C. Troncoso, Philip C. Wong, Paul F. Worley. Cell. 2011; 147(3): 615-628

One of the hallmarks of Alzheimer’s Disease is the accumulation of β amyloid peptide (Aβ) in the brain. The generation of Aβ is coupled to neuronal activity, however the molecular basis is unknown. This study by Wu et al. show that immediate early gene Arc, which plays an important role in multiple forms of neural plasticity, is also essential for Aβ generation, and functions by regulating γ-secretase trafficking via its direct binding to presenilin1. Genetic deletion of Arc reduces Aβ load in a transgenic mouse model of AD. In concert with the finding that Arc is increased in affected brain regions of AD patients.