One of the pathological hallmarks in brains of patients with Alzheimer's disease (AD) is the presence of neuritic plaques, in which amyloid deposits are surrounded by reactive gliosis and dystrophic neurites. Within neuritic plaques, reticulon 3 (RTN3), a homolog of Nogo protein, appears to regulate the formation of both amyloid deposition via negative modulation of BACE1 activity and dystrophic neurites via the formation of RTN3 aggregates. Transgenic mice over-expressing RTN3, but not the other known markers of dystrophic neurites in AD brain, spontaneously develop RTN3-immunoreactive dystrophic neurites. The presence of dystrophic neurites impairs cognition. Blocking abnormal RTN3 aggregation will increase the available RTN3 monomer and is therefore a promising therapeutic strategy for enhancing cognitive function in AD patients.