APOE and Alzheimer disease: The use of conventional or ‘novel’ pharmacological and immunological approaches in the literature is endemic with reports of repeated failures in AD clinical trials that target the neuropathological hallmarks of the AD process: amyloidogenesis, ApoE anomalies, tau-based hyperphosphorylation and neurofibrillary tangle formation, defective neurotropism, pro-inflammatory neuropathology and neuronal and synaptic atrophy and decline.