PSEN1 mutants promote neurodegeneration and dementia without any increase in Aβ, suggesting the causal roles of PSEN1 mutants in AD via an Aβ-independent manner [35–38]. PSEN1 mutations might progressively impair neurogenesis, which is closely related to the memory deficits and cognitive decline in AD [39]. Neurogenesis occurs in the hippocampus throughout life. Alterations in notch and wnt signaling, mutations in PSEN1 and APP, can impair the process of neurogenesis in AD [40]. Increase neurogensis or decreased neurogenesis happened in different stage of AD process [41]. Defection in maturation and reduction in the survival of newborn neurons, and compromised dendritic branching during neurogenesis are contributors to the cognition loss of AD [40]. Previous study found reduced hippocampal stem cells and higher DCX level in the dentate gyrus of AD patients’ brain [41]. We observed that the AD-NPCs grow slower than normal NPCs when transplanted to the hippocampus of immune-deficient mice (Supplementary Figure 5). Aβ accumulation has been considered as a late event in AD [42]. Here, we showed that the premature neuronal differentiation began earlier than the changes in Aβ42 and
