In summary, often, seemingly contradicting results were observed in apparently similar animal models. However, as this review reveals, there are numerous players in FAD that may modulate neurogenesis. Neurogenic roles have been attributed to both PS1 and APP. Each APP metabolite alone (e.g., sAPPα, APP-CTFs, p3, Aβ), as well as different conformation and aggregation levels of a given metabolite, such as Aβ, may have unique or specialized role and effect on aspects of neurogenesis. As a consequence, whether a mutation affects β- or γ-secretase activity may modulate neurogenesis differently. In addition, both α- and γ- and possibly β-secretase have numerous neurogenic substrates. Fibrillogenic Aβ levels and concentrations have been shown to have variable effects on neurogenesis. Extent of amyloid deposition and specific pattern of accumulation in the hippocampus may affect neurogenesis differently, as well as astrogliosis, microgliosis, synaptic degeneration and neuronal cell death. Furthermore, the method of neurogenic analysis must be comprehensive and consistent (e.g. BrdU regimen, cell markers, age, etc.) Thus, a thorough understanding of the molecular mechanism underlying AD is required for the analysis of neurogenesis in FAD
