APP and Alzheimer disease: All 4 human RTN proteins seem to be involved in AD, inasmuch as beta-site amyloid precursor protein-cleaving enzyme1 (BACE1), the β-secretase responsible for the cleavage of the amyloid precursor protein (APP) into β-amyloid peptide (Aβ) was found to co-immunoprecipitate with RTN1, RTN2, RTN3, and RTN4 (He et al. 2004).