Enlarged early endosomes are among the first cellular pathological features observed in AD pathogenesis (Cataldo et al., 2000, 2004; Nixon et al., 2000; Nixon, 2005), even prior to amyloid deposits in a given brain region, and AD-related enlarged early endosomes occur to a greater degree in the brains of APOE4 carriers (Cataldo et al., 2000). The gene discussed is APOE; the disease is Alzheimer disease.