APOE and Alzheimer disease: The ability of neurons to synthesize ApoE is constrained by ApoE immunoreactivity in cortical and hippocampal neurons of AD patients and the elderly For example: entorhinal cortex lesions (ECL) can damage the penetrating pathway in the hippocampus, causing a rapid increase in ApoE mRNA expression in the hippocampus (Poirier et al., 1991; Gómez-Ramos et al., 2001); ApoE binds to esterified cholesterol via the low-density lipoprotein receptor-associated protein (LPR) pathway after perceived entry into neurons (Holtzman et al., 1995).