APP and Alzheimer disease: Fundamental axonal pathology in AD includes the aberrant accumulation of various proteins in abnormal swollen axons, including APP (Cras et al., 1991), synaptic proteins like alpha-synuclein (Wirths et al., 2000), glycogen (Mann et al., 1987), as well as the occurrence of abnormal paired helical filaments (PHFs) (Praprotnik et al., 1996).