of the 42 residues of the Aβ) reduces amyloid deposition and enhances neurogenesis in PDAPP mice (Becker et al., 2007). Mirochnic and colleagues shows that experience of APP23 in enriched environment enhances neurogenesis, while reducing the ratio of Aβ42/Aβ40 (Mirochnic et al., 2009). While the majority of studies suggest that expression of FAD linked mutations compromise neurogenesis in the adult brain, the reaction of neurogenesis to alterations in the neuronal environment may induce temporally differential extent of neurogenesis. This is demonstrated well in a study of Chen and colleagues, which showed that conditional ablation of PS1 in the forebrain and knock out of PS2 in adult mice (PS1/PS2 KO mice) induces massive neurodegeneration in the cortex and hippocampus. This neurodegeneration is accompanied by induced cell proliferation in the SGL. However, most of these newly formed cells do not survive. In late stages of neurodegeneration the survival of newly generated neurons was severely impaired so that the enhanced neurogenesis could not be detected any more (Chen et al., 2008). This study shows that alterations in neurogenesis are neurodegenerative stage-dependent.
