APOE and Alzheimer disease: In addition, the facilitation of neurogenesis following environmental enrichment stimulation failed in the ApoE4-Tg mice, while it enhanced neurogenesis in the SGZ of ApoE3-Tg and wild-type mice [52,79].Therefore, the aforementioned studies show that the central molecular players in AD influence the generation of new hippocampal neurons, hence it is becoming evident that alterations in neurogenesis start even earlier than the onset of hallmark lesions or neuronal loss [22,80].