cells in the SGL of the hippocampus. These impairments were evident at one year of age, post-onset of deposition, but not at 2 months of age. Examination of newly-formed BrdU+DCX+ neuroblasts revealed their decrease in the SGL concomitantly with an increase in their number in the granule layer (Donovan et al., 2006), emphasize the necessity for a subregion-specific analysis for the assessment of the numbers of newly-formed cells in the hippocampal microenvironment, as well as the need for cell-lineage specific markers in addition to BrdU for a thorough analysis of neurogenesis. Similar observations were obtained in mice harboring FAD-linked mutant APPswe (double mutation). These studies revealed reduced extent of proliferation of newly formed cells and neuronal differentiation in the SGL of the dentate gyrus (Haughey et al., 2002a) and in the SVZ (Haughey et al., 2002b) in these mice. The APPswe transgene is ∼2.5 fold overexpressed compared to endogenous levels, and mice exhibit increased β-secretase activity, resulting in increased levels of β-CTF, Aβ and sAPPβ, concomitantly with lower levels of sAPPα (Thinakaran et al., 1996; Borchelt et al., 1996). All of these APP metabolites are thought to modulate variable aspects of neurogenesis, and thus the results of these studies suggest
